\u900f\u904e\u4e00\u7cfb\u5217\u7684\u7d50\u69cb\u6bd4\u5c0d\u5206\u6790\u53ef\u4ee5\u767c\u73fe\uff0c\u86cb\u767d\u7d10\u7d50\u69cb\u578b\u5728\u4e0d\u540c\u5bb6\u65cf\u7684\u6f14\u5316\u904e\u7a0b\u4e2d\uff0c\u591a\u534a\u5728\u4e00\u958b\u59cb\u4fbf\u88ab\u4fdd\u5b58\u4e0b\u4f86\u3002\u4ee5SPOUT\u548cUCH\u5bb6\u65cf\u70ba\u4f8b\uff0c\u76ee\u524d\u5df2\u77e5\u7684\u6240\u6709\u5bb6\u65cf\u6210\u54e1\u7684\u5206\u5b50\u7d50\u69cb\u4e2d\u90fd\u542b\u6709\u5171\u540c\u768431\u7d50\u548c52\u7d50\u69cb\u578b\u3002\u96d6\u7136SPOUT\u5bb6\u65cf\u6210\u54e1\u5df2\u6709\u76f8\u7576\u591a\u7684\u5206\u652f\uff0c\u5f7c\u6b64\u4e4b\u9593\u7684\u80fa\u57fa\u9178\u5e8f\u5217\u76f8\u4f3c\u5ea6\u4e5f\u6709\u9650\uff0c\u4f46\u662f\u6240\u6709\u6210\u54e1\u5747\u900f\u904e\u76f8\u540c\u7684\u7279\u6b8a31\u7d50\u69cb\u578b\u8fa8\u8b58\u53cd\u61c9\u57fa\u8ceaS-\u817a\u82f7-L-\u9ad8\u534a\u80f1\u6c28\u9178\uff08S-adenosyl-L-homocysteine, SAH\uff1b\u898b\u5716\u4e00B\uff09[5]\u3002\u540c\u6a23\u7684\uff0c\u50c5\u5728\u771f\u6838\u751f\u7269\u4e2d\u5b58\u5728\u7684UCH\u5bb6\u65cf\u6210\u54e1\uff0c\u5f9e\u9175\u6bcd\u83cc\u5230\u4eba\u985e\u90fd\u5177\u6709\u5171\u540c\u768452\u7d50\u69cb\u578b\uff0c\u800c\u5176N\u7aef\u4e5f\u662f\u8207\u6cdb\u7d20\u7d50\u5408\u7684\u91cd\u8981\u7d50\u69cb\u8fa8\u8b58\u7d44\u4ef6\u4e4b\u4e00[6]\u3002\u5728\u76ee\u524d\u5df2\u77e5\u7684\u7d10\u7d50\u86cb\u767d\u5bb6\u65cf\u4e2d\uff0c\u8106\u5f31\u64ec\u687f\u83cc\u7684N-\u7425\u73c0\u9170\u57fa-L-\u9ce5\u6c28\u9178\u8f49\u6c28\u7532\u9170\u9176\uff08Bacteroides fragilis N-succinyl-l-ornithine transcarbamylase, BfSOTC\uff09\u548c\u91ce\u6cb9\u83dc\u9ec3\u55ae\u80de\u83cc\u7684N-\u4e59\u9170\u57fa-L-\u9ce5\u6c28\u9178\u8f49\u6c28\u7532\u9170\u9176\uff08Xanthomonas campestris N-acetyl-l-ornithine transcarbamylase, XcAOTC\uff09\u662f\u552f\u4e00\u7531\u672a\u6253\u7d50\u7684\u9ce5\u6c28\u9178\u8f49\u6c28\u7532\u9170\u9176\u8d85\u7d1a\u5bb6\u65cf\u4e2d\u5206\u652f\u51fa\u4f86\u7684\u7d10\u7d50\u86cb\u767d\u6210\u54e1\u3002\u5982\u540c\u5176\u4ed6\u7d10\u7d50\u86cb\u767d\uff0cXcAOTC\u548cBfSOTC\u768431\u7d50\u7d50\u69cb\u4e5f\u6703\u53c3\u8207\u8fa8\u8b58\u7cbe\u6c28\u9178\uff08arginine\uff09\u53ca\u5c3f\u7d20\u751f\u5408\u6210\u524d\u9a45\u7269N-\u4e59\u9170\u57fa-L-\u9ce5\u6c28\u9178\u8f49\u6c28\u7532\u9170\u9176\uff08ARO\uff09\u3002XcAOTC\u80fd\u6709\u6548\u5730\u8fa8\u8b58ARO\u4e0a\u7684\u4e59\u9170\u57fa\u9032\u884c\u9ad8\u9078\u64c7\u6027\u7684\u9175\u7d20\u53cd\u61c9\uff1b\u76f8\u53cd\u7684\uff0c\u5927\u8178\u687f\u83cc\u7684L-\u9ce5\u6c28\u9178\u8f49\u6c28\u7532\u9170\u9176\uff08EcOTC\uff09\u5247\u7121\u6cd5\u6709\u6548\u8fa8\u8b58ARO\u984d\u5916\u7684\u4e59\u9170\u57fa\uff08\u898b\u5716\u4e00\uff22\uff09\u3002OTC\u8d85\u7d1a\u5bb6\u65cf\u4e5f\u5c31\u6210\u70ba\u4e86\u89e3\u86cb\u767d\u7d10\u7d50\u5728\u6f14\u5316\u4e0a\u529f\u80fd\u8207\u7d50\u69cb\u76f8\u95dc\u6027\u7684\u96e3\u5f97\u7684\u81ea\u7136\u751f\u7269\u7cfb\u7d71\u3002<\/p>\n
![\"\"](\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2018\/08\/4-1.jpg\")
\uff08\u5716\u4e00\uff09\u86cb\u767d\u8cea\u4e09\u7dad\u7d50\u69cb\u4e2d\u7d10\u7d50\u69cb\u578b\u7684\u5075\u6e2c\u4ee5\u53ca\u86cb\u767d\u7d10\u7d50\u53c3\u8207\u57fa\u8cea\u8fa8\u8b58\u4e4b\u7bc4\u4f8b\u3002\u5927\u591a\u6578\u86cb\u767d\u8cea\u7684\u4e09\u7dad\u7d50\u69cb\u932f\u7d9c\u8907\u96dc\uff0c\u4e0d\u5bb9\u6613\u4ee5\u8089\u773c\u5224\u65b7\u9aa8\u67b6\u647a\u758a\u4e4b\u62d3\u6a38\u69cb\u578b\u662f\u5426\u542b\u6709\u7d10\u7d50\u3002\u5176\u4e2d\u4e00\u500b\u86cb\u767d\u7d10\u7d50\u5075\u6e2c\u65b9\u5f0f\u662f\u900f\u904e\u56fa\u5b9a\u86cb\u767d\u8cea\u5206\u5b50\u69cb\u578b\u7684N\u7aef\u8207C\u7aef\u5750\u6a19\u5f8c\uff0c\u5c07\u9aa8\u67b6\u8def\u5f91\u5713\u6ed1\u7c21\u5316\uff0c\u4f46\u4ea4\u932f\u7684\u8def\u5f91\u4e0d\u80fd\u8de8\u8d8a\u5f7c\u6b64\u3002\u524d\u4ea4\u901a\u5927\u5b78\u9ec3\u93ae\u525b\u6559\u6388\u5f15\u9032\u8a72\u8a08\u7b97\u6cd5\u6240\u767c\u8868\u4e4b pKNOT\u7db2\u7ad9[7]\u53ef\u4ee5\u8b93\u4f7f\u7528\u8005\u4e0a\u50b3\u5df2\u77e5\u4e4b\u86cb\u767d\u8cea\u5206\u5b50\u7d50\u69cb\u5ea7\u6a19\uff0c\u5354\u52a9\u7c21\u5316\u9aa8\u67b6\u8def\u5f91\uff0c\u9032\u800c\u900f\u904e\u8996\u89ba\u8fa8\u8b58\u7d10\u7d50\u7684\u5b58\u5728\u3002\u5716A\u4ee5\u672c\u5be6\u9a57\u5ba4\u6240\u7814\u7a76\u4e4b\u5177\u670931\u7d50\u7684\u6d41\u611f\u55dc\u8840\u687f\u83cc\uff08Haemophilus influenzae\uff09RNA\u7532\u57fa\u8f49\u79fb\u9176YibK\u53ca52\u7d50\u7684\u4eba\u985eUCH-L1\u4f5c\u70ba\u7bc4\u4f8b\uff0c\u986f\u793a\u9aa8\u67b6\u8def\u5f91\u5713\u6ed1\u7a0b\u5e8f\u4e4b\u8a08\u7b97\u7d50\u679c\uff0c\u540c\u6642\u5728\u6700\u53f3\u65b9\u5716\u793a\u5c07N\u7aef\u8207C\u7aef\u4ee5\u865b\u7dda\u9023\u7d50\u5f8c\u5f62\u6210\u5c01\u9589\u8def\u5f91\u4ee5\u7b26\u5408\u6578\u5b78\u7d10\u7d50\u7406\u8ad6\u5b9a\u7fa9\u4e4b\u5716\u50cf\u63cf\u8ff0\u3002\u8a31\u591a\u86cb\u767d\u7d10\u7d50\u7d50\u69cb\u6703\u76f4\u63a5\u53c3\u8207\u8fa8\u8b58\u57fa\u8cea\u3002\u5716B\u5c07\u4e09\u500b\u5177\u4ee3\u8868\u6027\u7684\u7d10\u7d50\u86cb\u767d:YibK\u3001AOTC \u53caUCH-L1\u4ee5\u5361\u901a\u6a21\u5f0f\u5448\u73fe\u4e26\u5c07\u53c3\u8207\u7d10\u7d50\u69cb\u578b\u7684\u74b0\u72c0\u69cb\u578b\u986f\u793a\u70ba\u85cd\u8272\u4e26\u5c07\u7a7f\u904e\u8a72\u74b0\u72c0\u69cb\u578b\u7684\u9aa8\u67b6\u8def\u5f91\u986f\u793a\u70ba\u7d05\u8272\uff0c\u4e26\u5c07\u5176SAH\u53caARO\u5206\u5b50\u69cb\u578b\u4ee5\u6dfa\u85cd\u3001\u6df1\u85cd\u3001\u7d05\u8272\u53ca\u9ec3\u8272\u7403\u5f62\u986f\u793a\u78b3\u3001\u6c2e\u3001\u6c27\u53ca\u786b\u539f\u5b50\uff1b\u800cUCH-L1\u6240\u8fa8\u8b58\u4e4b\u6cdb\u7d20\u5206\u5b50\u5247\u4ee5\u534a\u900f\u660e\u8868\u9762\u6a21\u578b\u986f\u793a\u3002<\/p><\/div>\n
\u900f\u904e\u591a\u53c3\u6578\u7269\u7406\u5316\u5b78\u5206\u6790\u65b9\u6cd5\u5efa\u7acb\u7d10\u7d50\u86cb\u767d\u647a\u758a\u6a5f\u5236\u7406\u8ad6<\/strong><\/h2>\n\u81ea\u5f9e\u7d10\u7d50\u86cb\u767d\u5728\u7d50\u69cb\u8cc7\u6599\u5eab\u4e2d\u9678\u7e8c\u88ab\u767c\u73fe\u5f8c\uff0c\u5be6\u9a57\u8207\u7406\u8ad6\u5b78\u5bb6\u958b\u59cb\u63a2\u8a0e\u7d10\u7d50\u86cb\u767d\u7684\u6253\u7d50\u6a5f\u5236\u3002\u900f\u904e\u4e0d\u540c\u7a7a\u9593\u8207\u6642\u9593\u5c3a\u5ea6\u7684\u7406\u8ad6\u8a08\u7b97\uff0c\u6709\u4e09\u7a2e\u86cb\u767d\u8cea\u6253\u7d50\u6a5f\u5236\u88ab\u63d0\u51fa\uff0c\u5176\u4e2d\u5305\u62ec\u76f4\u63a5\u7a7f\u7dda\uff08direct threading\uff09\u3001\u6ed1\u52d5\u6253\u7d50\uff08slip-knotting\uff09\u548c\u6355\u9f20\u5668\u7ffb\u84cb\uff08mouse trapping\uff09\u7b49\u6a5f\u5236\u3002\u91dd\u5c0d\u7d10\u7d50\u86cb\u767d\u647a\u758a\u7684\u5be6\u9a57\u8cc7\u8a0a\u4e3b\u8981\u6e90\u8d77\u65bc\u82f1\u570b\u528d\u6a4b\u5927\u5b78Sophie Jackson\u5be6\u9a57\u5ba4\u65bc2005\u5e74\u958b\u59cb\u5c0d\u65bc\u5177\u670931\u7d50\u7684\u6d41\u611f\u55dc\u8840\u687f\u83cc\uff08Haemophilus influenzae\uff09RNA\u7532\u57fa\u8f49\u79fb\u9176YibK\u8207\u5927\u8178\u687f\u83cc\u7532\u57fa\u8f49\u79fb\u9176YbeA\u7684\u4e00\u7cfb\u5217\u7814\u7a76\u5de5\u4f5c\u3002\u8a72\u5718\u968a\u767c\u73fe\u9019\u5169\u500bSPOUT\u5bb6\u65cf\u6210\u54e1\u96d6\u7136\u6709\u76f8\u8fd1\u768431\u7d50\u69cb\u578b\uff0c\u4f46\u662f\u5176\u647a\u758a\u8def\u5f91\u76f8\u53bb\u751a\u9060[8]\u3002\u6709\u8da3\u7684\u662f\uff0cJackson\u7b49\u4eba\u6307\u51fa\uff0cYibK\u8207YbeA\u5728\u5916\u52a0\u5927\u91cf\u5c3f\u7d20\u5c0e\u81f4\u86cb\u767d\u8cea\u8b8a\u6027\u3001\u5931\u53bb\u4e8c\u7d1a\u8207\u4e09\u7d1a\u7d50\u69cb\u6642\uff0c\u4ecd\u820a\u8655\u65bc\u6253\u7d50\u7684\u72c0\u614b[9]\u3002\u6b64\u5916\uff0cYibK\u8207YbeA\u53ef\u4ee5\u5728\u5b8c\u6210\u751f\u5408\u6210\u96e2\u958b\u6838\u7cd6\u9ad4\u4e4b\u5f8c\uff0c\u81ea\u767c\u6027\u5730\u5b8c\u6210\u6253\u7d50\u72c0\u614b\uff1b\u5916\u52a0\u4f34\u96a8\u86cb\u767d\u9176\uff08molecular chaperone\uff09GroEL\/GroES\u5247\u6703\u5927\u5e45\u52a0\u901f\u9019\u5169\u500b\u6253\u7d50\u86cb\u767d\u7684\u647a\u758a\u901f\u7387[10]\u3002\u63db\u8a00\u4e4b\uff0c\u6709\u5225\u65bcDNA\u9700\u8981\u501f\u7531\u62d3\u6a38\u7570\u69cb\u9176\u7684\u5354\u52a9\u4ee5\u9054\u6210\u62d3\u6a38\u7d10\u7d50\u69cb\u578b\uff0c\u7d10\u7d50\u86cb\u767d\u53ef\u4ee5\u81ea\u767c\u6027\u5730\u5b8c\u6210\u7279\u6b8a\u4e14\u7dca\u7dfb\u7684\u7d10\u7d50\u72c0\u614b\u3002<\/p>\n
\u81ea2010\u8d77\uff0c\u672c\u5be6\u9a57\u5ba4\u5728\u4eba\u985e\u524d\u92d2\u79d1\u5b78\u7814\u7a76\u8a08\u5283\uff08Human Frontier Science Program\uff09\u53ca\u79d1\u6280\u90e8\u7684\u8cc7\u52a9\u4e0b\uff0c\u958b\u59cb\u7cfb\u7d71\u6027\u5730\u7814\u7a76\u7d10\u7d50\u86cb\u767d\u7684\u647a\u758a\u6a5f\u5236\uff0c\u900f\u904e\u591a\u53c3\u6578\u751f\u7269\u7269\u7406\u5316\u5b78\u65b9\u6cd5\uff0c\u6bd4\u8f03\u5206\u6790\u4e0d\u540c\u985e\u578b\u7d10\u7d50\u86cb\u767d\u4ee5\u53ca\u540c\u4e00\u5bb6\u65cf\u6210\u54e1\u7684\u7d10\u7d50\u86cb\u767d\u647a\u758a\u71b1\u529b\u5b78\u8207\u52d5\u529b\u5b78\u53c3\u6578\uff0c\u9032\u800c\u5efa\u7acb\u5404\u500b\u7d10\u7d50\u86cb\u767d\u69cb\u578b\u647a\u758a\u8def\u5f91\u81ea\u7531\u80fd\u666f\u89c0\uff08folding free energy landscape\uff09\u3002\u5176\u4e2d\u5305\u62ec\u5177\u6709\u6700\u5c0f31\u7d50\u7684\u55dc\u71b1\u83cc\uff08Methanocaldococcus jannaschii \uff09\u86cb\u767dMJ0366[11]\u53ca\u5177\u6709\u6700\u8907\u96dc61\u7d50\u7684\u60e1\u81ed\u5047\u55ae\u80de\u83cc\u9e75\u9178\u812b\u9e75\u7d20\u9176\uff08Pseudomonas putida haloacid dehalogenase, DehI\uff09[12]\u3002\u52a0\u4e0a\u91dd\u5c0d\u4eba\u985eUCH\u5bb6\u65cf\u6210\u54e1UCH-L1\u3001UCH-L3\u3001UCH-L5\u53caBAP1\u7684\u4e00\u7cfb\u5217\u6bd4\u8f03\u6027\u5206\u6790\uff0c\u6211\u5011\u767c\u73fe\u96d6\u7136\u4e0d\u540c\u985e\u578b\u7684\u7d10\u7d50\u86cb\u767d\u8cea\u5c0d\u65bc\u5916\u52a0\u7269\u7406\u5316\u5b78\u523a\u6fc0\uff08\u4f8b\u5982\u6eab\u5ea6\u4ee5\u53ca\u5316\u5b78\u7269\u8cea\uff09\u7684\u8010\u53d7\u5ea6\u5404\u6709\u4e0d\u540c\uff0c\u4f46\u6240\u6709\u7d10\u7d50\u86cb\u767d\u5728\u5c55\u958b\u69cb\u578b\u7684\u904e\u7a0b\u4e2d\uff0c\u90fd\u6703\u51fa\u73fe\u660e\u986f\u7684\u4e2d\u9593\u72c0\u614b\uff08intermediate state, I\uff09\u3002\u6709\u4e9b\u7d10\u7d50\u86cb\u767d\u53ef\u4ee5\u900f\u904e\u55ae\u4e00\u8def\u5f91\u5f62\u6210\u4e00\u500b\u7c21\u55ae\u7684\u4e2d\u9593\u72c0\u614b\uff0c\u6709\u4e9b\u7d10\u7d50\u86cb\u767d\uff08\u4f8b\u5982DehI\uff09\u6703\u5728\u540c\u4e00\u8def\u5f91\u4e0a\u51fa\u73fe\u5169\u7a2e\u4e0d\u540c\u7684\u4e2d\u9593\u72c0\u614b[12]\uff0c\u5176\u4ed6\u7d10\u7d50\u86cb\u767d\uff08\u4f8b\u5982UCH-L1\uff09\u5247\u6703\u900f\u904e\u5169\u689d\u5e73\u884c\u8def\u5f91\u5f62\u6210\u4e0d\u540c\u7684\u4e2d\u9593\u72c0\u614b\uff0c\u4e26\u5404\u81ea\u9023\u7d50\u81ea\u7136\u72c0\u614b\uff08native state, N\uff09\u8207\u8b8a\u6027\u72c0\u614b\uff08denatured state, D\uff09[13]\u3002\u86cb\u767d\u8cea\u647a\u758a\u904e\u7a0b\u4e2d\u51fa\u73fe\u986f\u8457\u4e2d\u9593\u72c0\u614b\u7684\u7d50\u679c\u986f\u793a\uff0c\u7d10\u7d50\u86cb\u767d\u69cb\u578b\u647a\u758a\u8def\u5f91\u81ea\u7531\u80fd\u666f\u89c0\u5145\u6eff\u80fd\u91cf\u9677\u9631\uff0c\u5c0e\u81f4\u7d10\u7d50\u86cb\u767d\u5f9e\u9ad8\u80fd\u91cf\u7684\u8b8a\u6027\u72c0\u614b\u8f49\u8b8a\u70ba\u4f4e\u80fd\u91cf\u7684\u81ea\u7136\u72c0\u614b\u904e\u7a0b\u4e2d\u5145\u6eff\u632b\u6298\uff08frustration\uff09\u3002\u9019\u500b\u89c0\u5bdf\u8207\u7406\u8ad6\u8a08\u7b97\u7406\u8ad6\u8a08\u7b97\u63d0\u51fa\u7d10\u7d50\u7684\u5f62\u6210\u662f\u7d10\u7d50\u86cb\u767d\u647a\u758a\u904e\u7a0b\u7684\u901f\u7387\u9650\u5236\u6b65\u9a5f\uff08rate-limiting step\uff09\u7684\u5047\u8aaa\u662f\u4e00\u81f4\u7684\u3002<\/p>\n
\u8207\u5e15\u91d1\u68ee\u6c0f\u75c7\u606f\u606f\u76f8\u95dc\u7684UCH-L1<\/strong><\/h2>\n\u5177\u670952\u7d50\u7684UCH-L1\u662f\u4eba\u985e\u8166\u795e\u7d93\u5143\u4e2d\u8868\u73fe\u91cf\u6700\u9ad8\u7684\u86cb\u767d\u8cea\u4e4b\u4e00\uff0cUCH-L1\u7d93\u5e38\u8207\u03b1-\u7a81\u89f8\u6838\u86cb\u767d\uff08\u03b1-synuclein\uff09\u4e00\u8d77\u51fa\u73fe\u5728\u5e15\u91d1\u68ee\u6c0f\u75c7\u60a3\u8005\u8166\u90e8\u7684\u8def\u6613\u6c0f\u9ad4\uff08Lewy body\uff09\u3002\u91dd\u5c0d\u5e15\u91d1\u68ee\u6c0f\u75c7\u5bb6\u65cf\u6027\u907a\u50b3I93M\u5c0d\u4eba\u985eUCH-L1\u9020\u6210\u7684\u7d50\u69cb\u3001\u52d5\u614b\u8207\u529f\u80fd\u7684\u5f71\u97ff\u9032\u884c\u5206\u5b50\u5c64\u9762\u7684\u5206\u6790\u3002\u96d6\u7136UCH-L1\u91ce\u751f\u7a2e\uff08wild type\uff09\u8207\u5e15\u91d1\u68ee\u6c0f\u75c7\u5bb6\u65cf\u907a\u50b3I93M\u7a81\u8b8a\u9ad4\u7684\u6676\u9ad4\u7d50\u69cb\u4e26\u7121\u660e\u986f\u5dee\u8ddd\uff0c\u672c\u5be6\u9a57\u5ba4\u900f\u904e\u6db2\u614b\u6838\u78c1\u5171\u632f\u5149\u8b5c\uff08nuclear magnetic resonance, NMR\uff09\u986f\u793aI93M\u7a81\u8b8a\u9020\u6210\u5c0dUCH-L1\u9175\u7d20\u53cd\u61c9\u4e2d\u5fc3\u4ee5\u53ca\u5468\u906d\u7684\u5316\u5b78\u74b0\u5883\u7522\u751f\u986f\u8457\u5f71\u97ff[14]\u3002\u672c\u5be6\u9a57\u5ba4\u8207Sophie Jackson\u5be6\u9a57\u5ba4\u5408\u4f5c\u4e26\u7d50\u5408NMR\u3001\u86cb\u767d\u8cea\u81ea\u9ad4\u87a2\u5149\u4ee5\u53ca\u5713\u4e8c\u8272\u65cb\u5149\uff08CD\uff09\u5149\u8b5c\u5206\u6790\u767c\u73feUCH-L1\u5728\u81ea\u7136\u72c0\u614b\u6642\u5373\u5b58\u5728\u8a31\u591a\u90e8\u5206\u5c55\u958b\u69cb\u578b\uff08partially unfolded forms, PUFs\uff09\uff0c\u800c\u5176\u7d50\u69cb\u7279\u6027\u8207\u900f\u904e\u5916\u52a0\u5c3f\u7d20\u5f15\u767c\u5316\u5b78\u8b8a\u6027\u53cd\u61c9\u7522\u751f\u4e2d\u9593\u72c0\u614b\u6709\u6975\u9ad8\u7684\u76f8\u4f3c\u5ea6[13]\u3002\u96d6\u7136\u86cb\u767d\u8cea\u647a\u758a\u53cd\u61c9\u4e2d\u9593\u72c0\u614b\u7684\u5206\u5b50\u69cb\u578b\u6c7a\u5b9a\u4e0d\u6613\uff0c\u4f46\u662f\u900f\u904e\u87a2\u5149\u5149\u8b5c\u5206\u6790\u53ef\u4ee5\u78ba\u77e5UCH-L1\u5728\u900f\u904e\u5316\u5b78\u7269\u8cea\u9a45\u4f7f\u69cb\u578b\u5c55\u958b\u7684\u904e\u7a0b\u4e2d\u6703\u7d93\u7531\u5169\u689d\u4e0d\u540c\u8def\u5f91\u7522\u751f\u4e0d\u540c\u7684\u4e2d\u9593\u72c0\u614b\uff08I\u53caI\u2019\uff09\uff0c\u9032\u800c\u5b8c\u5168\u5931\u53bb\u5176\u4e8c\u7d1a\u53ca\u4e09\u7d1a\u7d50\u69cb\uff0c\u6210\u70ba\u8b8a\u6027\u72c0\u614b\uff08\u898b\u5716\u4e8c\uff09\u3002\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0cNMR\u3001\u87a2\u5149\u53caCD\u5149\u8b5c\u53ea\u80fd\u53cd\u61c9\u4e0d\u540c\u7684\u7d50\u69cb\u8868\u5fb5\uff0c\u800c\u4e14\u9019\u4e9b\u7d50\u69cb\u8868\u5fb5\u591a\u534a\u70ba\u5c40\u90e8\u7d50\u69cb\u8cc7\u8a0a\uff0c\u56e0\u6b64\u5373\u4f7f\u6709\u9019\u4e9b\u4e0d\u540c\u7684\u7d50\u69cb\u8cc7\u8a0a\uff0c\u95e1\u8ff0\u86cb\u767d\u8cea\u69cb\u578b\u7522\u751f\u7684\u647a\u758a\u8def\u5f91\u4f9d\u820a\u6709\u778e\u5b50\u6478\u8c61\u7684\u4e0d\u5b8c\u6574\u6027\u3002\u672c\u5be6\u9a57\u5ba4\u5728\u8fd1\u65e5\u900f\u904e\u570b\u5bb6\u540c\u6b65\u8f3b\u5c04\u7814\u7a76\u4e2d\u5fc3\u4e4b\u5c0f\u89d2\u5ea6X\u5149\u6563\u5c04\uff08small angle X-ray scattering, SAXS\uff09\u5206\u6790\u65b9\u6cd5\u4ee5\u53ca\u591a\u89d2\u5ea6\u975c\u614b\u5149\u6563\u5c04\u7d50\u5408\u7dda\u4e0a\u5206\u5b50\u7be9\u5c64\u6790\u5206\u96e2\u6280\u8853\uff08size exclusion chromatography coupled multi-angle light scattering, SEC-MALS\uff09\uff0c\u8b49\u660e UCH-L1\u7684\u4e2d\u9593\u72c0\u614b\u5176\u5be6\u662f\u5177\u6709\u9ad8\u5ea6\u7d50\u69cb\u4e82\u5ea6\u7684\u4e8c\u805a\u9ad4\u8207\u56db\u805a\u9ad4\u3002\u5728\u79fb\u9664\u5316\u5b78\u8b8a\u6027\u7269\u8cea\u4e4b\u5f8c\uff0c\u4e2d\u9593\u72c0\u614b\u4e8c\u805a\u9ad4\u8207\u56db\u805a\u9ad4\u53ef\u4ee5\u56de\u5fa9\u5230\u4ee5\u55ae\u805a\u9ad4\u5f62\u5f0f\u5b58\u5728\u7684\u81ea\u7136\u72c0\u614b[15]\u3002\u4f46\u662f\u7576UCH-L1\u51fa\u73feI93M\u7a81\u8b8a\u4e4b\u5f8c\uff0c\u5916\u52a0\u5c3f\u7d20\u6703\u5c0e\u81f4UCH-L1\u805a\u96c6\u5f62\u6210\u975e\u5e38\u5927\u4e14\u7121\u5e8f\u7684\u805a\u96c6\u6c88\u6fb1\uff1b\u5728\u9ad8\u86cb\u767d\u6fc3\u5ea6\u7684\u60c5\u6cc1\u4e0b\uff0c\u5373\u4fbf\u4e8b\u5f8c\u79fb\u9664\u5916\u52a0\u5c3f\u7d20\u4e5f\u7121\u6cd5\u6709\u6548\u5c07UCH-L1\u5e36\u56de\u539f\u5148\u7684\u81ea\u7136\u72c0\u614b\u3002\u8a72\u767c\u73fe\u986f\u793aUCH-L1\u5176\u5be6\u5b58\u5728\u65bc\u4e9e\u7a69\u5b9a\u72c0\u614b\uff08metastable state\uff09\uff0c\u4efb\u4f55\u7a81\u8b8a\u53ca\u8f49\u8b6f\u5f8c\u4fee\u98fe\u90fd\u5f88\u5bb9\u6613\u7834\u58de\u5176\u7a69\u5b9a\u6027\u800c\u5f15\u767c\u932f\u8aa4\u647a\u758a\u8207\u805a\u96c6\u6c88\u6fb1\u7684\u73fe\u8c61\u3002\u9019\u500b\u767c\u73fe\u6216\u8a31\u53ef\u4ee5\u89e3\u91cb\u70ba\u4f55UCH-L1\u7d93\u5e38\u8207\u03b1-synuclein\u4e00\u8d77\u5806\u758a\u5728\u8def\u6613\u6c0f\u9ad4\u3002<\/p>\n
![\"\"](\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2018\/08\/4-2.jpg\")
\uff08\u5716\u4e8c\uff09\u900f\u904e\u591a\u91cd\u7269\u7406\u5316\u5b78\u53c3\u6578\u71b1\u529b\u5b78\u8207\u52d5\u529b\u5b78\u5206\u6790\u65b9\u6cd5\u5efa\u7acb\u4eba\u985eUCH-L1\u69cb\u578b\u647a\u758a\u8def\u5f91\u81ea\u7531\u80fd\u666f\u89c0\u3002<\/p><\/div>\n
\u7d10\u7d50\u63d0\u4f9b\u86cb\u767d\u8cea\u6975\u9ad8\u7684\u62d3\u6a38\u529b\u969c\u8207\u86cb\u767d\u9176\u9ad4\u62d4\u6cb3\u62b5\u6297\u5c55\u958b\u69cb\u578b\u7684\u5916\u529b<\/strong><\/h2>\n\u5728\u6bd4\u8f03\u4eba\u985eUCH-L1\u3001UCH-L3\u8207UCH-L5\u7684\u647a\u758a\u71b1\u529b\u5b78\u8207\u52d5\u529b\u5b78\u7684\u904e\u7a0b\u4e2d\uff0c\u6211\u5011\u767c\u73feUCH-L5\u5177\u6709\u6975\u70ba\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\uff08intrinsic unfolding rate\uff09\u3002\u4e00\u822c\u800c\u8a00\uff0c\u7a69\u5b9a\u7684\u86cb\u767d\u8cea\u5177\u6709\u8f03\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\uff0c\u800c\u5176\u69cb\u578b\u5728\u81ea\u7136\u72c0\u614b\u4e0b\u4e5f\u76f8\u5c0d\u6709\u8f03\u5c11\u7684\u52d5\u614b\u8207\u7d50\u69cb\u8b8a\u7570\u3002\u4f46\u662f\u900f\u904e\u6bd4\u5c0dUCH-L5\u7684NMR\u6c2b\u6c18\u4ea4\u63db\u8207\u87a2\u5149\u5be6\u9a57\u6578\u64da\uff0c\u6211\u5011\u767c\u73feUCH-L5\u5728\u81ea\u7136\u72c0\u614b\u4e0b\u5b58\u5728\u6bd4UCH-L1\u53caUCH-L3\u90fd\u9084\u8981\u66f4\u52a0\u660e\u986f\u7684\u5340\u57df\u6027\u7d50\u69cb\u71b1\u64fe\u52d5\uff08thermal fluctuation\uff09\uff0c\u4f46\u5176\u6574\u9ad4\u71b1\u529b\u5b78\u7a69\u5b9a\u6027\u537b\u6bd4\u53e6\u5916\u5169\u500bUCH\u5bb6\u65cf\u6210\u54e1\u8981\u9ad8\u51fa\u8a31\u591a\uff0c\u5176\u69cb\u578b\u5c55\u958b\u52d5\u529b\u5b78\u53cd\u61c9\u901f\u7387\u4e5f\u6bd4UCH-L1\u6162\u4e86\u8fd1\u4e00\u842c\u500d\u3002\u5f9e\u71b1\u529b\u5b78\u7684\u89d2\u5ea6\u4f86\u770b\uff0c\u7cfb\u7d71\u7684\u7a69\u5b9a\u6027\u9664\u4e86\u900f\u904e\u9375\u7d50\uff08\u7113\uff09\u7a69\u5b9a\u69cb\u578b\u4e4b\u5916\uff0c\u4e5f\u53ef\u4ee5\u900f\u904e\u589e\u52a0\u7cfb\u7d71\u4e82\u5ea6\uff08\u71b5\uff09\u4f86\u964d\u4f4e\u81ea\u7531\u80fd\u3002\u7531\u65bcUCH-L5\u7684\u6cdb\u7d20C\u7aef\u6c34\u89e3\u529f\u80fd\u9700\u8981\u900f\u904e\u8207\u86cb\u767d\u9176\u9ad4\uff08proteasome\uff09\u4e0a\u7684\u6cdb\u7d20\u53d7\u5668\uff08Rpn13\uff09\u7d50\u5408\u4e4b\u5f8c\u624d\u6703\u88ab\u6d3b\u5316\uff0c\u6b64\u5916\uff0cUCH-L5\u4e5f\u9700\u8207\u86cb\u767d\u9176\u9ad4\u7af6\u722d\u540c\u4e00\u500b\u88ab\u6cdb\u7d20\u5316\u7684\u57fa\u8cea\uff0cUCH-L5\u57fa\u672c\u4e0a\u662f\u8207\u6301\u7e8c\u900f\u904e\u6c34\u89e3\u4e09\u78f7\u9178\u817a\u82f7\uff08ATP\uff09\u7522\u751f\u5916\u529b\u5c55\u958b\u6cdb\u7d20\u5316\u57fa\u8cea\u7684\u86cb\u767d\u9176\u9ad4\u9032\u884c\u62d4\u6cb3\u3002\u56e0\u6b64\u6211\u5011\u63a8\u6e2cUCH-L5\u768452\u7d50\u4ee5\u53ca\u5176\u6975\u70ba\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\u61c9\u8a72\u6703\u63d0\u4f9bUCH-L5\u8f03\u9ad8\u7684\u529b\u5b78\u7a69\u5b9a\u6027\u3002<\/p>\n
\u70ba\u4e86\u8b49\u660e\u9019\u500b\u5047\u8aaa\uff0c\u6211\u5011\u5229\u7528\u5927\u8178\u687f\u83cc\u7684\u86cb\u767d\u9176\u9ad4ClpXP\u4f5c\u70ba\u6a21\u5f0f\u7cfb\u7d71\uff0c\u6e2c\u8a66UCH\u5bb6\u65cf\u6210\u54e1\u7684\u529b\u5b78\u7a69\u5b9a\u6027\u3002\u900f\u904e\u86cb\u767d\u8cea\u5de5\u7a0b\u6280\u8853\uff0c\u5c07\u5e36\u670911\u500b\u80fa\u57fa\u9178\u7684ssrA\u5e8f\u5217\uff08AANDENYALAA\uff1b\u5716\u4e2d\u929c\u63a5\u65bcUCH\u78b3\u7aef\u7684\u7d05\u8272\u7247\u6bb5\uff09\u6a19\u8a18\u5728UCH\u7684C\u7aef\uff0c ClpX\u74b0\u72c0\u516d\u805a\u9ad4\u53ef\u4ee5\u8fa8\u8b58ssrA\u5e8f\u5217\uff0c\u4e26\u900f\u904e\u6c34\u89e3ATP\u7522\u751f\u5916\u529b\u5c55\u958b\u57fa\u8cea\u4e4b\u7acb\u9ad4\u69cb\u578b\u6210\u70ba\u7dda\u6027\u591a\u80bd\u93c8\uff0c\u63a5\u8457\u88ab\u9001\u5165\u7531\u96d9\u5c64\u74b0\u72c0\u4e03\u805a\u9ad4\u6240\u5f62\u6210\u7684\u5c01\u9589\u7a7a\u9593\u9032\u884c\u55ae\u4e00\u65b9\u5411\u4e14\u5177\u9ad8\u5ea6\u6301\u7e8c\u6027\uff08processivity\uff09\u7684\u6c34\u89e3\u53cd\u61c9\u5c07\u57fa\u8cea\u5206\u89e3\uff1b\u63db\u8a00\u4e4b\uff0cClpP\u5fc5\u9808\u6709\u6548\u5730\u900f\u904e\u6c34\u89e3ATP\u7522\u751f\u8108\u885d\u5f0f\u7684\u62c9\u529b\uff0c\u5c07\u5177\u6709C\u7aefssrA\u6a19\u8a18\u7684\u57fa\u8cea\u86cb\u767d\u5c55\u958b\u6210\u7dda\u6027\u591a\u80bd\u93c8\u4ee5\u8de8\u8d8aClpXP\u9175\u7d20\u52d5\u529b\u5b78\u7684\u901f\u7387\u9650\u5236\u6b65\u9a5f\u3002ClpXP\u7684\u9175\u7d20\u52d5\u529b\u5b78\u4ee5\u53caATP\u6c34\u89e3\u6240\u7522\u751f\u4e4b\u529b\u5b78\u5c55\u958b\u57fa\u8cea\u86cb\u767d\u5206\u5b50\u6a5f\u5236\u5728\u6587\u737b\u5747\u6709\u8a73\u7d30\u8a18\u8f09\uff0c\u5176\u4e2d\uff0c\u5177\u5099\u9ad8\u5ea6\u71b1\u7a69\u5b9a\u6027\uff08\u8b8a\u6eab\u6eab\u5ea6Tm > 85 \u00b0C\uff09\u53ca\u5316\u5b78\u7a69\u5b9a\u6027\u4e4b\u7da0\u8272\u87a2\u5149\u86cb\u767d\uff08GFP\uff09\u662f\u6700\u5e38\u88ab\u7528\u70ba\u6a19\u6e96\u57fa\u8cea\u7684\u9078\u64c7\u4e4b\u4e00\u3002\u76f8\u8f03\u65bcGFP\uff0c\u4eba\u985eUCH-L1\u3001UCH-L3\u3001UCH-L5\u53caBAP1\u572845-55 \u00b0C\u4ee5\u53ca\u76f8\u5c0d\u5c11\u91cf\u7684\u5316\u5b78\u8b8a\u6027\u7269\u8cea\uff08\u4f8b\u5982\u5c3f\u7d20\uff09\u4fbf\u6703\u9010\u6f38\u5931\u53bb\u5176\u5206\u5b50\u69cb\u578b\u7684\u7a69\u5b9a\u6027\u3002\u5373\u4fbf\u5982\u6b64\uff0c\u6211\u5011\u767c\u73feUCH-L1\u8207UCH-L5\u53d7\u5230ClpXP\u5916\u529b\u5c55\u958b\u7d50\u69cb\u9032\u800c\u88ab\u6c34\u89e3\u7684\u53cd\u61c9\u901f\u7387\u8f03GFP\u6162\u4e86\u4e00\u767e\u81f3\u4e00\u842c\u500d\uff0c\u986f\u793a\u9019\u5169\u500bUCH\u5206\u5b50\u5177\u6709\u6975\u9ad8\u7684\u529b\u5b78\u7a69\u5b9a\u6027[16]\u3002\u6211\u5011\u66f4\u9032\u4e00\u6b65\u900f\u904e\u526a\u77edUCH-L1\u7684N\u7aef\u5341\u4e00\u500b\u80fa\u57fa\u9178\u4ee5\u89e3\u958b\u517652\u7d10\u7d50\u69cb\u578b\uff08UCH-L1\uf04411\uff1b\u8acb\u53c3\u898b\u5716\u3127B\u4e4bUCH-L1\u5206\u5b50\u6a21\u578b\uff0c\u5176\u6c2e\u7aef\u7684\u6578\u500b\u80fa\u57fa\u9178\u5f62\u621052\u7d10\u7d50\u69cb\u578b\u7684\u5143\u4ef6\u4e4b\u4e00\uff09\u800c\u986f\u8457\u52a0\u901fClpXP\u7684\u53cd\u61c9\u901f\u7387\u8b49\u660eUCH-L1\u7684\u62d3\u6a38\u529b\u969c\u662f\u5c0e\u81f4ClpX\u7121\u6cd5\u6709\u6548\u5c55\u958b\u5176\u4e09\u7dad\u7a7a\u9593\u5206\u5b50\u69cb\u578b\u7684\u4e3b\u56e0\u4e4b\u4e00\u3002UCH-L5\u56e0\u6b64\u6210\u70ba\u73fe\u4eca\u6587\u737b\u5831\u5c0e\u4e2d\u6700\u80fd\u6709\u6548\u6291\u5236ClpXP\u65bd\u52a0\u5916\u529b\u5c55\u958b\u57fa\u8cea\u69cb\u578b\u7684\u86cb\u767d\u8cea\u3002<\/p>\n
![\"\"](\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2018\/08\/4-3.jpg\")
\uff08\u5716\u4e09\uff09\u5229\u7528\u5927\u8178\u687f\u83cc\u4e4bClpXP\u86cb\u767d\u8cea\u5c55\u958b\u9176\uff0f\u6c34\u89e3\u9176\u932f\u5408\u7269\u8a55\u91cf52\u7d10\u7d50\u69cb\u578b\u5c0d\u65bcUCH\u5bb6\u65cf\u86cb\u767d\u8cea\u6210\u54e1\u529b\u5b78\u7a69\u5b9a\u6027\u8ca2\u737b\u5be6\u9a57\u8a2d\u8a08\u793a\u610f\u5716\u3002<\/p><\/div>\n
\u7d50\u8a9e<\/strong><\/h2>\n\u7d10\u7d50\u86cb\u767d\u8cea\u5b58\u5728\u65bc\u81ea\u7136\u754c\u5404\u500b\u7269\u7a2e\u4e4b\u4e2d\uff0c\u5176\u4e09\u7dad\u7a7a\u9593\u69cb\u578b\u8207\u62d3\u6a38\u5404\u6709\u4e0d\u540c\u3002\u900f\u904e\u5206\u6790\u73fe\u4eca\u4e0a\u5343\u7b46\u7d10\u7d50\u86cb\u767d\u7684\u7d50\u69cb\u8207\u76f8\u4f3c\u5bb6\u65cf\u6210\u54e1\u7684\u5e8f\u5217\u6bd4\u5c0d\uff0c\u61c9\u8a72\u53ef\u4ee5\u7aba\u898b\u504f\u597d\u7d10\u7d50\u5f62\u6210\u7684\u5e8f\u5217\u7279\u6027\uff0c\u7136\u800c\u9019\u9805\u751f\u7269\u8cc7\u8a0a\u5206\u6790\u5de5\u4f5c\u4ecd\u6709\u5f85\u5c08\u5bb6\u5617\u8a66\u3002\u5f9e\u86cb\u767d\u8cea\u5f62\u6210\u7d10\u7d50\u7684\u6a5f\u5236\u5206\u6790\u7814\u7a76\u5de5\u4f5c\u4f86\u770b\uff0c\u900f\u904e\u672c\u5be6\u9a57\u5ba4\u8207\u5176\u4ed6\u7406\u8ad6\u8207\u5be6\u9a57\u5b78\u5bb6\u7684\u5171\u540c\u52aa\u529b\uff0c\u6211\u5011\u5c0d\u65bc\u7d10\u7d50\u86cb\u767d\u7684\u5f62\u6210\u7684\u5206\u5b50\u6a5f\u5236\uff0c\u751f\u7269\u610f\u7fa9\u4ee5\u53ca\u5c0d\u61c9\u4e0d\u540c\u7269\u7406\u5316\u5b78\u8b8a\u6578\uff08\u5305\u542b\u6eab\u5ea6\u3001\u5316\u5b78\u80fd\u4ee5\u53ca\u5916\u529b\uff09\u7684\u7a69\u5b9a\u6027\u5df2\u9010\u6f38\u6709\u6240\u4e86\u89e3\u3002\u7136\u800c\uff0c\u5982\u540c\u672c\u6587\u6240\u8ff0\uff0c\u5373\u4fbf\u900f\u904e\u5404\u5f0f\u5404\u6a23\u751f\u7269\u7269\u7406\u5206\u6790\u65b9\u6cd5\u53d6\u5f97\u95dc\u65bc\u7d10\u7d50\u86cb\u767d\u8cea\u7684\u7d50\u69cb\u8cc7\u8a0a\uff0c\u95e1\u8ff0\u86cb\u767d\u8cea\u69cb\u578b\u7522\u751f\u7684\u647a\u758a\u8def\u5f91\u4f9d\u820a\u6709\u778e\u5b50\u6478\u8c61\u7684\u4e0d\u5b8c\u6574\u6027\u3002\u70ba\u4e86\u80fd\u6709\u66f4\u5168\u9762\u7684\u5be6\u9a57\u8cc7\u8a0a\u63d0\u4f9b\u7406\u8ad6\u8a08\u7b97\u505a\u4ea4\u53c9\u6bd4\u5c0d\uff0c\u672c\u5be6\u9a57\u5ba4\u7a4d\u6975\u5f15\u5165\u65b0\u7a4e\u5be6\u9a57\u6280\u8853\u63d0\u5347\u86cb\u767d\u8cea\u7d50\u69cb\u5206\u6790\u7684\u6642\u9593\u8207\u7a7a\u9593\u89e3\u6790\u5ea6\u3002\u4e2d\u592e\u7814\u7a76\u9662\u5167\u7684\u751f\u7269\u7269\u7406\u6838\u5fc3\u8a2d\u65bd\uff0c\u9ad8\u78c1\u5834\u6838\u78c1\u5171\u632f\u5149\u8b5c\u6838\u5fc3\u8a2d\u65bd\u4ee5\u53ca\u751f\u5316\u6240\u8cea\u8b5c\u6838\u5fc3\u8a2d\u65bd\u6700\u8fd1\u5f15\u9032\u7684\u6c2b\u6c18\u4ea4\u63db\u8cea\u8b5c\u5206\u6790\u65b9\u6cd5\uff0c\u63d0\u4f9b\u4e86\u6700\u4f73\u7684\u6280\u8853\u652f\u63f4\u3002\u6211\u5011\u671f\u671b\u5728\u672a\u4f86\u80fd\u501f\u91cd\u5982\u6b64\u5b8c\u5584\u7684\u7814\u7a76\u8a2d\u65bd\u5c0d\u65bc\u7d10\u7d50\u86cb\u767d\u8cea\u7684\u751f\u7269\u529f\u80fd\u8207\u62d3\u6a38\u7d10\u7d50\u7684\u76f8\u95dc\u6027\u7372\u5f97\u66f4\u6df1\u5165\u7684\u8a8d\u77e5\uff0c\u9032\u800c\u4e86\u89e3\u5927\u81ea\u7136\u70ba\u4f55\u5927\u8cbb\u5468\u7ae0\u6f14\u5316\u51fa\u5982\u6b64\u8907\u96dc\u7684\u7d50\u69cb\u3002<\/p>\n
\u53c3\u8003\u6587\u737b<\/strong><\/h2>\n[1] J.S. Richardson, b-Sheet topology and the relatedness of proteins, Nature, 268 (1977) 495-500.<\/p>\n
[2] M.L. Mansfield, Are there knots in proteins?, Nat. Struc. Biol., 1 (1994) 213-214.<\/p>\n
[3] M. Jamroz, W. Niemyska, E.J. Rawdon, A. Stasiak, K.C. Millett, P. Sulkowski, J.I. Sulkowska, KnotProt: a database of proteins with knots and slipknots, Nucleic Acids Res., 43 (2015) D306-314.<\/p>\n
[4] S.E. Jackson, A. Suma, C. Micheletti, How to fold intricately: using theory and experiments to unravel the properties of knotted proteins, Curr. Opin. Struct. Biol., 42 (2017) 6-14.<\/p>\n
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[6] S.-T.D. Hsu, Folding Dynamics and Structural Basis of the Enzyme Mechanism of Ubiquitin C-Terminal Hydroylases, in: A. Svendsen (Ed.) Understanding enzymes – function, design, engineering and analysis, Pan Stanford Publishing, Singapore, 2016, pp. 167-202.<\/p>\n
[7] Y.L. Lai, C.C. Chen, J.K. Hwang, pKNOT v.2: the protein KNOT web server, Nucleic Acids Res., 40 (2012) W228-231.<\/p>\n
[8] A.L. Mallam, S.E. Jackson, Probing nature’s knots: the folding pathway of a knotted homodimeric protein, J. Mol. Biol., 359 (2006) 1420-1436.<\/p>\n
[9] A.L. Mallam, J.M. Rogers, S.E. Jackson, Experimental detection of knotted conformations in denatured proteins, Proc. Natl. Acad. Sci. U. S. A., 107 (2010) 8189-8194.<\/p>\n
[10] A.L. Mallam, S.E. Jackson, Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins, Nat. Chem. Biol., 8 (2012) 147-153.<\/p>\n
[11] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Unraveling the folding mechanism of the smallest knotted protein, MJ0366, J. Phys. Chem. B, 119 (2015) 4359-4370.<\/p>\n
[12] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Folding analysis of the most complex Stevedore’s protein knot, Sci. Rep., 6 (2016) 31514.<\/p>\n
[13] S.-C. Lou, S. Wetzel, H. Zhang, E.W. Crone, Y.-T. Lee, S.E. Jackson, S.-T.D. Hsu, The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates, J. Mol. Biol., 428 (2016) 2507-2520.<\/p>\n
[14] S.M. Kumar, P.C. Lyu, S.-T.D. Hsu, Structural perturbation of the Parkinson\u2019s disease-associated I93M mutation in human UCH-L1 revealed by solution state NMR spectroscopy, Chinese J. Magn. Reson., 32 (2015) 329-340.<\/p>\n
[15] Y.C. Lee, S.D. Hsu, A natively monomeric deubiquitinase UCH-L1 forms highly dynamic but defined metastable oligomeric folding intermediates, J. Phys. Chem. Lett., 9 (2018) 2433-2437.<\/p>\n
[16] M.K. Sriramoju, Y. Chen, Y.C. Lee, S.-T.D. Hsu, Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease, Sci. Rep., 8 (2018) 7076.<\/p>\n
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\u5177\u670952\u7d50\u7684UCH-L1\u662f\u4eba\u985e\u8166\u795e\u7d93\u5143\u4e2d\u8868\u73fe\u91cf\u6700\u9ad8\u7684\u86cb\u767d\u8cea\u4e4b\u4e00\uff0cUCH-L1\u7d93\u5e38\u8207\u03b1-\u7a81\u89f8\u6838\u86cb\u767d\uff08\u03b1-synuclein\uff09\u4e00\u8d77\u51fa\u73fe\u5728\u5e15\u91d1\u68ee\u6c0f\u75c7\u60a3\u8005\u8166\u90e8\u7684\u8def\u6613\u6c0f\u9ad4\uff08Lewy body\uff09\u3002\u91dd\u5c0d\u5e15\u91d1\u68ee\u6c0f\u75c7\u5bb6\u65cf\u6027\u907a\u50b3I93M\u5c0d\u4eba\u985eUCH-L1\u9020\u6210\u7684\u7d50\u69cb\u3001\u52d5\u614b\u8207\u529f\u80fd\u7684\u5f71\u97ff\u9032\u884c\u5206\u5b50\u5c64\u9762\u7684\u5206\u6790\u3002\u96d6\u7136UCH-L1\u91ce\u751f\u7a2e\uff08wild type\uff09\u8207\u5e15\u91d1\u68ee\u6c0f\u75c7\u5bb6\u65cf\u907a\u50b3I93M\u7a81\u8b8a\u9ad4\u7684\u6676\u9ad4\u7d50\u69cb\u4e26\u7121\u660e\u986f\u5dee\u8ddd\uff0c\u672c\u5be6\u9a57\u5ba4\u900f\u904e\u6db2\u614b\u6838\u78c1\u5171\u632f\u5149\u8b5c\uff08nuclear magnetic resonance, NMR\uff09\u986f\u793aI93M\u7a81\u8b8a\u9020\u6210\u5c0dUCH-L1\u9175\u7d20\u53cd\u61c9\u4e2d\u5fc3\u4ee5\u53ca\u5468\u906d\u7684\u5316\u5b78\u74b0\u5883\u7522\u751f\u986f\u8457\u5f71\u97ff[14]\u3002\u672c\u5be6\u9a57\u5ba4\u8207Sophie Jackson\u5be6\u9a57\u5ba4\u5408\u4f5c\u4e26\u7d50\u5408NMR\u3001\u86cb\u767d\u8cea\u81ea\u9ad4\u87a2\u5149\u4ee5\u53ca\u5713\u4e8c\u8272\u65cb\u5149\uff08CD\uff09\u5149\u8b5c\u5206\u6790\u767c\u73feUCH-L1\u5728\u81ea\u7136\u72c0\u614b\u6642\u5373\u5b58\u5728\u8a31\u591a\u90e8\u5206\u5c55\u958b\u69cb\u578b\uff08partially unfolded forms, PUFs\uff09\uff0c\u800c\u5176\u7d50\u69cb\u7279\u6027\u8207\u900f\u904e\u5916\u52a0\u5c3f\u7d20\u5f15\u767c\u5316\u5b78\u8b8a\u6027\u53cd\u61c9\u7522\u751f\u4e2d\u9593\u72c0\u614b\u6709\u6975\u9ad8\u7684\u76f8\u4f3c\u5ea6[13]\u3002\u96d6\u7136\u86cb\u767d\u8cea\u647a\u758a\u53cd\u61c9\u4e2d\u9593\u72c0\u614b\u7684\u5206\u5b50\u69cb\u578b\u6c7a\u5b9a\u4e0d\u6613\uff0c\u4f46\u662f\u900f\u904e\u87a2\u5149\u5149\u8b5c\u5206\u6790\u53ef\u4ee5\u78ba\u77e5UCH-L1\u5728\u900f\u904e\u5316\u5b78\u7269\u8cea\u9a45\u4f7f\u69cb\u578b\u5c55\u958b\u7684\u904e\u7a0b\u4e2d\u6703\u7d93\u7531\u5169\u689d\u4e0d\u540c\u8def\u5f91\u7522\u751f\u4e0d\u540c\u7684\u4e2d\u9593\u72c0\u614b\uff08I\u53caI\u2019\uff09\uff0c\u9032\u800c\u5b8c\u5168\u5931\u53bb\u5176\u4e8c\u7d1a\u53ca\u4e09\u7d1a\u7d50\u69cb\uff0c\u6210\u70ba\u8b8a\u6027\u72c0\u614b\uff08\u898b\u5716\u4e8c\uff09\u3002\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0cNMR\u3001\u87a2\u5149\u53caCD\u5149\u8b5c\u53ea\u80fd\u53cd\u61c9\u4e0d\u540c\u7684\u7d50\u69cb\u8868\u5fb5\uff0c\u800c\u4e14\u9019\u4e9b\u7d50\u69cb\u8868\u5fb5\u591a\u534a\u70ba\u5c40\u90e8\u7d50\u69cb\u8cc7\u8a0a\uff0c\u56e0\u6b64\u5373\u4f7f\u6709\u9019\u4e9b\u4e0d\u540c\u7684\u7d50\u69cb\u8cc7\u8a0a\uff0c\u95e1\u8ff0\u86cb\u767d\u8cea\u69cb\u578b\u7522\u751f\u7684\u647a\u758a\u8def\u5f91\u4f9d\u820a\u6709\u778e\u5b50\u6478\u8c61\u7684\u4e0d\u5b8c\u6574\u6027\u3002\u672c\u5be6\u9a57\u5ba4\u5728\u8fd1\u65e5\u900f\u904e\u570b\u5bb6\u540c\u6b65\u8f3b\u5c04\u7814\u7a76\u4e2d\u5fc3\u4e4b\u5c0f\u89d2\u5ea6X\u5149\u6563\u5c04\uff08small angle X-ray scattering, SAXS\uff09\u5206\u6790\u65b9\u6cd5\u4ee5\u53ca\u591a\u89d2\u5ea6\u975c\u614b\u5149\u6563\u5c04\u7d50\u5408\u7dda\u4e0a\u5206\u5b50\u7be9\u5c64\u6790\u5206\u96e2\u6280\u8853\uff08size exclusion chromatography coupled multi-angle light scattering, SEC-MALS\uff09\uff0c\u8b49\u660e UCH-L1\u7684\u4e2d\u9593\u72c0\u614b\u5176\u5be6\u662f\u5177\u6709\u9ad8\u5ea6\u7d50\u69cb\u4e82\u5ea6\u7684\u4e8c\u805a\u9ad4\u8207\u56db\u805a\u9ad4\u3002\u5728\u79fb\u9664\u5316\u5b78\u8b8a\u6027\u7269\u8cea\u4e4b\u5f8c\uff0c\u4e2d\u9593\u72c0\u614b\u4e8c\u805a\u9ad4\u8207\u56db\u805a\u9ad4\u53ef\u4ee5\u56de\u5fa9\u5230\u4ee5\u55ae\u805a\u9ad4\u5f62\u5f0f\u5b58\u5728\u7684\u81ea\u7136\u72c0\u614b[15]\u3002\u4f46\u662f\u7576UCH-L1\u51fa\u73feI93M\u7a81\u8b8a\u4e4b\u5f8c\uff0c\u5916\u52a0\u5c3f\u7d20\u6703\u5c0e\u81f4UCH-L1\u805a\u96c6\u5f62\u6210\u975e\u5e38\u5927\u4e14\u7121\u5e8f\u7684\u805a\u96c6\u6c88\u6fb1\uff1b\u5728\u9ad8\u86cb\u767d\u6fc3\u5ea6\u7684\u60c5\u6cc1\u4e0b\uff0c\u5373\u4fbf\u4e8b\u5f8c\u79fb\u9664\u5916\u52a0\u5c3f\u7d20\u4e5f\u7121\u6cd5\u6709\u6548\u5c07UCH-L1\u5e36\u56de\u539f\u5148\u7684\u81ea\u7136\u72c0\u614b\u3002\u8a72\u767c\u73fe\u986f\u793aUCH-L1\u5176\u5be6\u5b58\u5728\u65bc\u4e9e\u7a69\u5b9a\u72c0\u614b\uff08metastable state\uff09\uff0c\u4efb\u4f55\u7a81\u8b8a\u53ca\u8f49\u8b6f\u5f8c\u4fee\u98fe\u90fd\u5f88\u5bb9\u6613\u7834\u58de\u5176\u7a69\u5b9a\u6027\u800c\u5f15\u767c\u932f\u8aa4\u647a\u758a\u8207\u805a\u96c6\u6c88\u6fb1\u7684\u73fe\u8c61\u3002\u9019\u500b\u767c\u73fe\u6216\u8a31\u53ef\u4ee5\u89e3\u91cb\u70ba\u4f55UCH-L1\u7d93\u5e38\u8207\u03b1-synuclein\u4e00\u8d77\u5806\u758a\u5728\u8def\u6613\u6c0f\u9ad4\u3002<\/p>\n
\uff08\u5716\u4e8c\uff09\u900f\u904e\u591a\u91cd\u7269\u7406\u5316\u5b78\u53c3\u6578\u71b1\u529b\u5b78\u8207\u52d5\u529b\u5b78\u5206\u6790\u65b9\u6cd5\u5efa\u7acb\u4eba\u985eUCH-L1\u69cb\u578b\u647a\u758a\u8def\u5f91\u81ea\u7531\u80fd\u666f\u89c0\u3002<\/p><\/div>\n
\u7d10\u7d50\u63d0\u4f9b\u86cb\u767d\u8cea\u6975\u9ad8\u7684\u62d3\u6a38\u529b\u969c\u8207\u86cb\u767d\u9176\u9ad4\u62d4\u6cb3\u62b5\u6297\u5c55\u958b\u69cb\u578b\u7684\u5916\u529b<\/strong><\/h2>\n\u5728\u6bd4\u8f03\u4eba\u985eUCH-L1\u3001UCH-L3\u8207UCH-L5\u7684\u647a\u758a\u71b1\u529b\u5b78\u8207\u52d5\u529b\u5b78\u7684\u904e\u7a0b\u4e2d\uff0c\u6211\u5011\u767c\u73feUCH-L5\u5177\u6709\u6975\u70ba\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\uff08intrinsic unfolding rate\uff09\u3002\u4e00\u822c\u800c\u8a00\uff0c\u7a69\u5b9a\u7684\u86cb\u767d\u8cea\u5177\u6709\u8f03\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\uff0c\u800c\u5176\u69cb\u578b\u5728\u81ea\u7136\u72c0\u614b\u4e0b\u4e5f\u76f8\u5c0d\u6709\u8f03\u5c11\u7684\u52d5\u614b\u8207\u7d50\u69cb\u8b8a\u7570\u3002\u4f46\u662f\u900f\u904e\u6bd4\u5c0dUCH-L5\u7684NMR\u6c2b\u6c18\u4ea4\u63db\u8207\u87a2\u5149\u5be6\u9a57\u6578\u64da\uff0c\u6211\u5011\u767c\u73feUCH-L5\u5728\u81ea\u7136\u72c0\u614b\u4e0b\u5b58\u5728\u6bd4UCH-L1\u53caUCH-L3\u90fd\u9084\u8981\u66f4\u52a0\u660e\u986f\u7684\u5340\u57df\u6027\u7d50\u69cb\u71b1\u64fe\u52d5\uff08thermal fluctuation\uff09\uff0c\u4f46\u5176\u6574\u9ad4\u71b1\u529b\u5b78\u7a69\u5b9a\u6027\u537b\u6bd4\u53e6\u5916\u5169\u500bUCH\u5bb6\u65cf\u6210\u54e1\u8981\u9ad8\u51fa\u8a31\u591a\uff0c\u5176\u69cb\u578b\u5c55\u958b\u52d5\u529b\u5b78\u53cd\u61c9\u901f\u7387\u4e5f\u6bd4UCH-L1\u6162\u4e86\u8fd1\u4e00\u842c\u500d\u3002\u5f9e\u71b1\u529b\u5b78\u7684\u89d2\u5ea6\u4f86\u770b\uff0c\u7cfb\u7d71\u7684\u7a69\u5b9a\u6027\u9664\u4e86\u900f\u904e\u9375\u7d50\uff08\u7113\uff09\u7a69\u5b9a\u69cb\u578b\u4e4b\u5916\uff0c\u4e5f\u53ef\u4ee5\u900f\u904e\u589e\u52a0\u7cfb\u7d71\u4e82\u5ea6\uff08\u71b5\uff09\u4f86\u964d\u4f4e\u81ea\u7531\u80fd\u3002\u7531\u65bcUCH-L5\u7684\u6cdb\u7d20C\u7aef\u6c34\u89e3\u529f\u80fd\u9700\u8981\u900f\u904e\u8207\u86cb\u767d\u9176\u9ad4\uff08proteasome\uff09\u4e0a\u7684\u6cdb\u7d20\u53d7\u5668\uff08Rpn13\uff09\u7d50\u5408\u4e4b\u5f8c\u624d\u6703\u88ab\u6d3b\u5316\uff0c\u6b64\u5916\uff0cUCH-L5\u4e5f\u9700\u8207\u86cb\u767d\u9176\u9ad4\u7af6\u722d\u540c\u4e00\u500b\u88ab\u6cdb\u7d20\u5316\u7684\u57fa\u8cea\uff0cUCH-L5\u57fa\u672c\u4e0a\u662f\u8207\u6301\u7e8c\u900f\u904e\u6c34\u89e3\u4e09\u78f7\u9178\u817a\u82f7\uff08ATP\uff09\u7522\u751f\u5916\u529b\u5c55\u958b\u6cdb\u7d20\u5316\u57fa\u8cea\u7684\u86cb\u767d\u9176\u9ad4\u9032\u884c\u62d4\u6cb3\u3002\u56e0\u6b64\u6211\u5011\u63a8\u6e2cUCH-L5\u768452\u7d50\u4ee5\u53ca\u5176\u6975\u70ba\u7de9\u6162\u7684\u81ea\u767c\u6027\u69cb\u578b\u5c55\u958b\u901f\u7387\u61c9\u8a72\u6703\u63d0\u4f9bUCH-L5\u8f03\u9ad8\u7684\u529b\u5b78\u7a69\u5b9a\u6027\u3002<\/p>\n
\u70ba\u4e86\u8b49\u660e\u9019\u500b\u5047\u8aaa\uff0c\u6211\u5011\u5229\u7528\u5927\u8178\u687f\u83cc\u7684\u86cb\u767d\u9176\u9ad4ClpXP\u4f5c\u70ba\u6a21\u5f0f\u7cfb\u7d71\uff0c\u6e2c\u8a66UCH\u5bb6\u65cf\u6210\u54e1\u7684\u529b\u5b78\u7a69\u5b9a\u6027\u3002\u900f\u904e\u86cb\u767d\u8cea\u5de5\u7a0b\u6280\u8853\uff0c\u5c07\u5e36\u670911\u500b\u80fa\u57fa\u9178\u7684ssrA\u5e8f\u5217\uff08AANDENYALAA\uff1b\u5716\u4e2d\u929c\u63a5\u65bcUCH\u78b3\u7aef\u7684\u7d05\u8272\u7247\u6bb5\uff09\u6a19\u8a18\u5728UCH\u7684C\u7aef\uff0c ClpX\u74b0\u72c0\u516d\u805a\u9ad4\u53ef\u4ee5\u8fa8\u8b58ssrA\u5e8f\u5217\uff0c\u4e26\u900f\u904e\u6c34\u89e3ATP\u7522\u751f\u5916\u529b\u5c55\u958b\u57fa\u8cea\u4e4b\u7acb\u9ad4\u69cb\u578b\u6210\u70ba\u7dda\u6027\u591a\u80bd\u93c8\uff0c\u63a5\u8457\u88ab\u9001\u5165\u7531\u96d9\u5c64\u74b0\u72c0\u4e03\u805a\u9ad4\u6240\u5f62\u6210\u7684\u5c01\u9589\u7a7a\u9593\u9032\u884c\u55ae\u4e00\u65b9\u5411\u4e14\u5177\u9ad8\u5ea6\u6301\u7e8c\u6027\uff08processivity\uff09\u7684\u6c34\u89e3\u53cd\u61c9\u5c07\u57fa\u8cea\u5206\u89e3\uff1b\u63db\u8a00\u4e4b\uff0cClpP\u5fc5\u9808\u6709\u6548\u5730\u900f\u904e\u6c34\u89e3ATP\u7522\u751f\u8108\u885d\u5f0f\u7684\u62c9\u529b\uff0c\u5c07\u5177\u6709C\u7aefssrA\u6a19\u8a18\u7684\u57fa\u8cea\u86cb\u767d\u5c55\u958b\u6210\u7dda\u6027\u591a\u80bd\u93c8\u4ee5\u8de8\u8d8aClpXP\u9175\u7d20\u52d5\u529b\u5b78\u7684\u901f\u7387\u9650\u5236\u6b65\u9a5f\u3002ClpXP\u7684\u9175\u7d20\u52d5\u529b\u5b78\u4ee5\u53caATP\u6c34\u89e3\u6240\u7522\u751f\u4e4b\u529b\u5b78\u5c55\u958b\u57fa\u8cea\u86cb\u767d\u5206\u5b50\u6a5f\u5236\u5728\u6587\u737b\u5747\u6709\u8a73\u7d30\u8a18\u8f09\uff0c\u5176\u4e2d\uff0c\u5177\u5099\u9ad8\u5ea6\u71b1\u7a69\u5b9a\u6027\uff08\u8b8a\u6eab\u6eab\u5ea6Tm > 85 \u00b0C\uff09\u53ca\u5316\u5b78\u7a69\u5b9a\u6027\u4e4b\u7da0\u8272\u87a2\u5149\u86cb\u767d\uff08GFP\uff09\u662f\u6700\u5e38\u88ab\u7528\u70ba\u6a19\u6e96\u57fa\u8cea\u7684\u9078\u64c7\u4e4b\u4e00\u3002\u76f8\u8f03\u65bcGFP\uff0c\u4eba\u985eUCH-L1\u3001UCH-L3\u3001UCH-L5\u53caBAP1\u572845-55 \u00b0C\u4ee5\u53ca\u76f8\u5c0d\u5c11\u91cf\u7684\u5316\u5b78\u8b8a\u6027\u7269\u8cea\uff08\u4f8b\u5982\u5c3f\u7d20\uff09\u4fbf\u6703\u9010\u6f38\u5931\u53bb\u5176\u5206\u5b50\u69cb\u578b\u7684\u7a69\u5b9a\u6027\u3002\u5373\u4fbf\u5982\u6b64\uff0c\u6211\u5011\u767c\u73feUCH-L1\u8207UCH-L5\u53d7\u5230ClpXP\u5916\u529b\u5c55\u958b\u7d50\u69cb\u9032\u800c\u88ab\u6c34\u89e3\u7684\u53cd\u61c9\u901f\u7387\u8f03GFP\u6162\u4e86\u4e00\u767e\u81f3\u4e00\u842c\u500d\uff0c\u986f\u793a\u9019\u5169\u500bUCH\u5206\u5b50\u5177\u6709\u6975\u9ad8\u7684\u529b\u5b78\u7a69\u5b9a\u6027[16]\u3002\u6211\u5011\u66f4\u9032\u4e00\u6b65\u900f\u904e\u526a\u77edUCH-L1\u7684N\u7aef\u5341\u4e00\u500b\u80fa\u57fa\u9178\u4ee5\u89e3\u958b\u517652\u7d10\u7d50\u69cb\u578b\uff08UCH-L1\uf04411\uff1b\u8acb\u53c3\u898b\u5716\u3127B\u4e4bUCH-L1\u5206\u5b50\u6a21\u578b\uff0c\u5176\u6c2e\u7aef\u7684\u6578\u500b\u80fa\u57fa\u9178\u5f62\u621052\u7d10\u7d50\u69cb\u578b\u7684\u5143\u4ef6\u4e4b\u4e00\uff09\u800c\u986f\u8457\u52a0\u901fClpXP\u7684\u53cd\u61c9\u901f\u7387\u8b49\u660eUCH-L1\u7684\u62d3\u6a38\u529b\u969c\u662f\u5c0e\u81f4ClpX\u7121\u6cd5\u6709\u6548\u5c55\u958b\u5176\u4e09\u7dad\u7a7a\u9593\u5206\u5b50\u69cb\u578b\u7684\u4e3b\u56e0\u4e4b\u4e00\u3002UCH-L5\u56e0\u6b64\u6210\u70ba\u73fe\u4eca\u6587\u737b\u5831\u5c0e\u4e2d\u6700\u80fd\u6709\u6548\u6291\u5236ClpXP\u65bd\u52a0\u5916\u529b\u5c55\u958b\u57fa\u8cea\u69cb\u578b\u7684\u86cb\u767d\u8cea\u3002<\/p>\n
\uff08\u5716\u4e09\uff09\u5229\u7528\u5927\u8178\u687f\u83cc\u4e4bClpXP\u86cb\u767d\u8cea\u5c55\u958b\u9176\uff0f\u6c34\u89e3\u9176\u932f\u5408\u7269\u8a55\u91cf52\u7d10\u7d50\u69cb\u578b\u5c0d\u65bcUCH\u5bb6\u65cf\u86cb\u767d\u8cea\u6210\u54e1\u529b\u5b78\u7a69\u5b9a\u6027\u8ca2\u737b\u5be6\u9a57\u8a2d\u8a08\u793a\u610f\u5716\u3002<\/p><\/div>\n
\u7d50\u8a9e<\/strong><\/h2>\n\u7d10\u7d50\u86cb\u767d\u8cea\u5b58\u5728\u65bc\u81ea\u7136\u754c\u5404\u500b\u7269\u7a2e\u4e4b\u4e2d\uff0c\u5176\u4e09\u7dad\u7a7a\u9593\u69cb\u578b\u8207\u62d3\u6a38\u5404\u6709\u4e0d\u540c\u3002\u900f\u904e\u5206\u6790\u73fe\u4eca\u4e0a\u5343\u7b46\u7d10\u7d50\u86cb\u767d\u7684\u7d50\u69cb\u8207\u76f8\u4f3c\u5bb6\u65cf\u6210\u54e1\u7684\u5e8f\u5217\u6bd4\u5c0d\uff0c\u61c9\u8a72\u53ef\u4ee5\u7aba\u898b\u504f\u597d\u7d10\u7d50\u5f62\u6210\u7684\u5e8f\u5217\u7279\u6027\uff0c\u7136\u800c\u9019\u9805\u751f\u7269\u8cc7\u8a0a\u5206\u6790\u5de5\u4f5c\u4ecd\u6709\u5f85\u5c08\u5bb6\u5617\u8a66\u3002\u5f9e\u86cb\u767d\u8cea\u5f62\u6210\u7d10\u7d50\u7684\u6a5f\u5236\u5206\u6790\u7814\u7a76\u5de5\u4f5c\u4f86\u770b\uff0c\u900f\u904e\u672c\u5be6\u9a57\u5ba4\u8207\u5176\u4ed6\u7406\u8ad6\u8207\u5be6\u9a57\u5b78\u5bb6\u7684\u5171\u540c\u52aa\u529b\uff0c\u6211\u5011\u5c0d\u65bc\u7d10\u7d50\u86cb\u767d\u7684\u5f62\u6210\u7684\u5206\u5b50\u6a5f\u5236\uff0c\u751f\u7269\u610f\u7fa9\u4ee5\u53ca\u5c0d\u61c9\u4e0d\u540c\u7269\u7406\u5316\u5b78\u8b8a\u6578\uff08\u5305\u542b\u6eab\u5ea6\u3001\u5316\u5b78\u80fd\u4ee5\u53ca\u5916\u529b\uff09\u7684\u7a69\u5b9a\u6027\u5df2\u9010\u6f38\u6709\u6240\u4e86\u89e3\u3002\u7136\u800c\uff0c\u5982\u540c\u672c\u6587\u6240\u8ff0\uff0c\u5373\u4fbf\u900f\u904e\u5404\u5f0f\u5404\u6a23\u751f\u7269\u7269\u7406\u5206\u6790\u65b9\u6cd5\u53d6\u5f97\u95dc\u65bc\u7d10\u7d50\u86cb\u767d\u8cea\u7684\u7d50\u69cb\u8cc7\u8a0a\uff0c\u95e1\u8ff0\u86cb\u767d\u8cea\u69cb\u578b\u7522\u751f\u7684\u647a\u758a\u8def\u5f91\u4f9d\u820a\u6709\u778e\u5b50\u6478\u8c61\u7684\u4e0d\u5b8c\u6574\u6027\u3002\u70ba\u4e86\u80fd\u6709\u66f4\u5168\u9762\u7684\u5be6\u9a57\u8cc7\u8a0a\u63d0\u4f9b\u7406\u8ad6\u8a08\u7b97\u505a\u4ea4\u53c9\u6bd4\u5c0d\uff0c\u672c\u5be6\u9a57\u5ba4\u7a4d\u6975\u5f15\u5165\u65b0\u7a4e\u5be6\u9a57\u6280\u8853\u63d0\u5347\u86cb\u767d\u8cea\u7d50\u69cb\u5206\u6790\u7684\u6642\u9593\u8207\u7a7a\u9593\u89e3\u6790\u5ea6\u3002\u4e2d\u592e\u7814\u7a76\u9662\u5167\u7684\u751f\u7269\u7269\u7406\u6838\u5fc3\u8a2d\u65bd\uff0c\u9ad8\u78c1\u5834\u6838\u78c1\u5171\u632f\u5149\u8b5c\u6838\u5fc3\u8a2d\u65bd\u4ee5\u53ca\u751f\u5316\u6240\u8cea\u8b5c\u6838\u5fc3\u8a2d\u65bd\u6700\u8fd1\u5f15\u9032\u7684\u6c2b\u6c18\u4ea4\u63db\u8cea\u8b5c\u5206\u6790\u65b9\u6cd5\uff0c\u63d0\u4f9b\u4e86\u6700\u4f73\u7684\u6280\u8853\u652f\u63f4\u3002\u6211\u5011\u671f\u671b\u5728\u672a\u4f86\u80fd\u501f\u91cd\u5982\u6b64\u5b8c\u5584\u7684\u7814\u7a76\u8a2d\u65bd\u5c0d\u65bc\u7d10\u7d50\u86cb\u767d\u8cea\u7684\u751f\u7269\u529f\u80fd\u8207\u62d3\u6a38\u7d10\u7d50\u7684\u76f8\u95dc\u6027\u7372\u5f97\u66f4\u6df1\u5165\u7684\u8a8d\u77e5\uff0c\u9032\u800c\u4e86\u89e3\u5927\u81ea\u7136\u70ba\u4f55\u5927\u8cbb\u5468\u7ae0\u6f14\u5316\u51fa\u5982\u6b64\u8907\u96dc\u7684\u7d50\u69cb\u3002<\/p>\n
\u53c3\u8003\u6587\u737b<\/strong><\/h2>\n[1] J.S. Richardson, b-Sheet topology and the relatedness of proteins, Nature, 268 (1977) 495-500.<\/p>\n
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[15] Y.C. Lee, S.D. Hsu, A natively monomeric deubiquitinase UCH-L1 forms highly dynamic but defined metastable oligomeric folding intermediates, J. Phys. Chem. Lett., 9 (2018) 2433-2437.<\/p>\n
[16] M.K. Sriramoju, Y. Chen, Y.C. Lee, S.-T.D. Hsu, Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease, Sci. Rep., 8 (2018) 7076.<\/p>\n
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\u53c3\u8003\u6587\u737b<\/strong><\/h2>\n[1] J.S. Richardson, b-Sheet topology and the relatedness of proteins, Nature, 268 (1977) 495-500.<\/p>\n
[2] M.L. Mansfield, Are there knots in proteins?, Nat. Struc. Biol., 1 (1994) 213-214.<\/p>\n
[3] M. Jamroz, W. Niemyska, E.J. Rawdon, A. Stasiak, K.C. Millett, P. Sulkowski, J.I. Sulkowska, KnotProt: a database of proteins with knots and slipknots, Nucleic Acids Res., 43 (2015) D306-314.<\/p>\n
[4] S.E. Jackson, A. Suma, C. Micheletti, How to fold intricately: using theory and experiments to unravel the properties of knotted proteins, Curr. Opin. Struct. Biol., 42 (2017) 6-14.<\/p>\n
[5] K.L. Tkaczuk, S. Dunin-Horkawicz, E. Purta, J.M. Bujnicki, Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases, BMC Bioinformatics, 8 (2007) 73.<\/p>\n
[6] S.-T.D. Hsu, Folding Dynamics and Structural Basis of the Enzyme Mechanism of Ubiquitin C-Terminal Hydroylases, in: A. Svendsen (Ed.) Understanding enzymes – function, design, engineering and analysis, Pan Stanford Publishing, Singapore, 2016, pp. 167-202.<\/p>\n
[7] Y.L. Lai, C.C. Chen, J.K. Hwang, pKNOT v.2: the protein KNOT web server, Nucleic Acids Res., 40 (2012) W228-231.<\/p>\n
[8] A.L. Mallam, S.E. Jackson, Probing nature’s knots: the folding pathway of a knotted homodimeric protein, J. Mol. Biol., 359 (2006) 1420-1436.<\/p>\n
[9] A.L. Mallam, J.M. Rogers, S.E. Jackson, Experimental detection of knotted conformations in denatured proteins, Proc. Natl. Acad. Sci. U. S. A., 107 (2010) 8189-8194.<\/p>\n
[10] A.L. Mallam, S.E. Jackson, Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins, Nat. Chem. Biol., 8 (2012) 147-153.<\/p>\n
[11] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Unraveling the folding mechanism of the smallest knotted protein, MJ0366, J. Phys. Chem. B, 119 (2015) 4359-4370.<\/p>\n
[12] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Folding analysis of the most complex Stevedore’s protein knot, Sci. Rep., 6 (2016) 31514.<\/p>\n
[13] S.-C. Lou, S. Wetzel, H. Zhang, E.W. Crone, Y.-T. Lee, S.E. Jackson, S.-T.D. Hsu, The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates, J. Mol. Biol., 428 (2016) 2507-2520.<\/p>\n
[14] S.M. Kumar, P.C. Lyu, S.-T.D. Hsu, Structural perturbation of the Parkinson\u2019s disease-associated I93M mutation in human UCH-L1 revealed by solution state NMR spectroscopy, Chinese J. Magn. Reson., 32 (2015) 329-340.<\/p>\n
[15] Y.C. Lee, S.D. Hsu, A natively monomeric deubiquitinase UCH-L1 forms highly dynamic but defined metastable oligomeric folding intermediates, J. Phys. Chem. Lett., 9 (2018) 2433-2437.<\/p>\n
[16] M.K. Sriramoju, Y. Chen, Y.C. Lee, S.-T.D. Hsu, Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease, Sci. Rep., 8 (2018) 7076.<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
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[1] J.S. Richardson, b-Sheet topology and the relatedness of proteins, Nature, 268 (1977) 495-500.<\/p>\n
[2] M.L. Mansfield, Are there knots in proteins?, Nat. Struc. Biol., 1 (1994) 213-214.<\/p>\n
[3] M. Jamroz, W. Niemyska, E.J. Rawdon, A. Stasiak, K.C. Millett, P. Sulkowski, J.I. Sulkowska, KnotProt: a database of proteins with knots and slipknots, Nucleic Acids Res., 43 (2015) D306-314.<\/p>\n
[4] S.E. Jackson, A. Suma, C. Micheletti, How to fold intricately: using theory and experiments to unravel the properties of knotted proteins, Curr. Opin. Struct. Biol., 42 (2017) 6-14.<\/p>\n
[5] K.L. Tkaczuk, S. Dunin-Horkawicz, E. Purta, J.M. Bujnicki, Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases, BMC Bioinformatics, 8 (2007) 73.<\/p>\n
[6] S.-T.D. Hsu, Folding Dynamics and Structural Basis of the Enzyme Mechanism of Ubiquitin C-Terminal Hydroylases, in: A. Svendsen (Ed.) Understanding enzymes – function, design, engineering and analysis, Pan Stanford Publishing, Singapore, 2016, pp. 167-202.<\/p>\n
[7] Y.L. Lai, C.C. Chen, J.K. Hwang, pKNOT v.2: the protein KNOT web server, Nucleic Acids Res., 40 (2012) W228-231.<\/p>\n
[8] A.L. Mallam, S.E. Jackson, Probing nature’s knots: the folding pathway of a knotted homodimeric protein, J. Mol. Biol., 359 (2006) 1420-1436.<\/p>\n
[9] A.L. Mallam, J.M. Rogers, S.E. Jackson, Experimental detection of knotted conformations in denatured proteins, Proc. Natl. Acad. Sci. U. S. A., 107 (2010) 8189-8194.<\/p>\n
[10] A.L. Mallam, S.E. Jackson, Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins, Nat. Chem. Biol., 8 (2012) 147-153.<\/p>\n
[11] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Unraveling the folding mechanism of the smallest knotted protein, MJ0366, J. Phys. Chem. B, 119 (2015) 4359-4370.<\/p>\n
[12] I. Wang, S.-Y. Chen, S.-T.D. Hsu, Folding analysis of the most complex Stevedore’s protein knot, Sci. Rep., 6 (2016) 31514.<\/p>\n
[13] S.-C. Lou, S. Wetzel, H. Zhang, E.W. Crone, Y.-T. Lee, S.E. Jackson, S.-T.D. Hsu, The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates, J. Mol. Biol., 428 (2016) 2507-2520.<\/p>\n
[14] S.M. Kumar, P.C. Lyu, S.-T.D. Hsu, Structural perturbation of the Parkinson\u2019s disease-associated I93M mutation in human UCH-L1 revealed by solution state NMR spectroscopy, Chinese J. Magn. Reson., 32 (2015) 329-340.<\/p>\n
[15] Y.C. Lee, S.D. Hsu, A natively monomeric deubiquitinase UCH-L1 forms highly dynamic but defined metastable oligomeric folding intermediates, J. Phys. Chem. Lett., 9 (2018) 2433-2437.<\/p>\n
[16] M.K. Sriramoju, Y. Chen, Y.C. Lee, S.-T.D. Hsu, Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease, Sci. Rep., 8 (2018) 7076.<\/p>\n
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