{"id":32225,"date":"2023-08-24T00:11:53","date_gmt":"2023-08-23T16:11:53","guid":{"rendered":"https:\/newsletter.sinica.edu.tw\/?p=32225"},"modified":"2023-08-25T11:17:54","modified_gmt":"2023-08-25T03:17:54","slug":"%e3%80%90%e5%b0%88%e6%ac%84%e3%80%91%e6%b7%ba%e8%ab%87%e8%9b%8b%e7%99%bd%e8%b3%aa%e7%9a%84%e8%a8%ad%e8%a8%88","status":"publish","type":"post","link":"https:\/newsletter.sinica.edu.tw\/32225\/","title":{"rendered":"\u3010\u5c08\u6b04\u3011\u6dfa\u8ac7\u86cb\u767d\u8cea\u7684\u8a2d\u8a08"},"content":{"rendered":"<div class=\"auth-info\">\n<div class='one_fourth'>\n\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" src=\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_A-1.jpg\" alt=\"\u4f5c\u8005\uff1a\u5433\u6606\u5cef\u52a9\u7814\u7a76\u54e1\uff08\u672c\u9662\u751f\u7269\u5316\u5b78\u7814\u7a76\u6240\uff09\" width=\"150\" height=\"150\" class=\"aligncenter size-full wp-image-32226\" \/>\n\t\t\t\t<\/div>\n<div class='three_fourth et_column_last'>\n\t\t\t\t\t\u4f5c\u8005\u70ba\u7f8e\u570b Rutgers \u5927\u5b78\u5316\u5b78\u8207\u5316\u5b78\u751f\u7269\u7cfb\u535a\u58eb\u3002\u6574\u5929\u8207\u86cb\u767d\u8cea\u70ba\u4f0d\uff0c\u4ee5\u4e86\u89e3\u86cb\u767d\u8cea\u7684\u529f\u80fd\u3001\u8a2d\u8a08\uff0f\u4fee\u6539\u86cb\u767d\u8cea\u6297\u79a6\u75be\u75c5\u70ba\u7814\u7a76\u65b9\u5411\u3002\u5728\u86cb\u767d\u8cea\u5316\u5b78\u5c08\u696d\u5916\uff0c\u662f\u696d\u9918\u8cde\u9ce5\u651d\u5f71\u611b\u597d\u8005\uff0c\u91cd\u5ea6\u68d2\u7403\u611b\u597d\u8005\u3002\n\t\t\t\t<\/div><div class='clear'><\/div><\/div>\n<p><strong>\u86cb\u767d\u8cea\u662f\u600e\u9ebc\u4f86\u7684\u5462\uff1f<\/strong><\/p>\n<p>\u86cb\u767d\u8cea\u662f\u4ec0\u9ebc\uff1f\u80fd\u5403\u55ce\uff1f\u86cb\u767d\u8cea\uff0c\u662f\u4e00\u7a2e\u751f\u7269\u5de8\u5206\u5b50\u3002\u86cb\u767d\u8cea\u662f\u751f\u7269\u8cf4\u4ee5\u7dad\u751f\u7684\u91cd\u8981\u7269\u8cea\uff0c\u5176\u82f1\u6587\u300cprotein\u300d\u662f 19 \u4e16\u7d00\u745e\u5178\u5316\u5b78\u5bb6 J\u00f6ns Jacob Berzelius \u6240\u767c\u660e\u7684 <sup>1<\/sup>\u3002 Berzelius \u6839\u64da\u8377\u862d\u79d1\u5b78\u5bb6 Gerardus Johannes Mulder \u5206\u6790\u86cb\u767d\u8cea\u7684\u7d44\u6210\u662f\u7531\u78b3\u3001\u6c2b\u3001\u6c27\u3001\u6c2e\u3001\u786b\u8207\u78f7\u7684\u5171\u540c\u7d44\u5408\uff0c\u4e26\u4ee5\u5e0c\u81d8\u5b57\u300c\u03c0\u03c1\u03ce\u03c4\u03b5\u03b9\u03bf\u03c2\uff08proteios\uff09\u300d\u70ba\u5b57\u6e90\uff0c\u610f\u5373\u4e3b\u8981\uff08primary\uff09\uff0c\u5b9a\u7fa9\u70ba\u300cprotein\u300d\u3002<\/p>\n<p>\u800c\u86cb\u767d\u8cea\u7684\u4e2d\u6587\u547d\u540d\uff0c\u9867\u540d\u601d\u7fa9\u662f\u8ddf\u96de\u86cb\u4e2d\u7684\u300c\u86cb\u767d\u300d\u6709\u95dc\uff0c\u4e00\u9846\u96de\u86cb\u7684\u86cb\u767d\u662f\u7531 9 \u6210\u7684\u6c34\u5206\u8207 1 \u6210\u7684\u86cb\u767d\u8cea\u7d44\u6210\uff0c\u53ef\u898b\u86cb\u767d\u8cea\u5728\u751f\u7406\u4e0a\u7684\u91cd\u8981\u6027\u3002\u86cb\u767d\u8cea\u8207\u6838\u9178\u90fd\u662f\u751f\u7269\u9ad4\u5167\u91cd\u8981\u7684\u6210\u5206\u3002\u5206\u5b50\u751f\u7269\u5b78\u7684\u4e2d\u5fc3\u7406\u8ad6\u63d0\u51fa\u907a\u50b3\u5bc6\u78bc\u6703\u5f9e DNA \u8f49\u9304\u5230 RNA\uff0c\u518d\u5f9e RNA \u8f49\u8b6f\u5230\u86cb\u767d\u8cea\u3002\u4eba\u985e\u57fa\u56e0\u7d44\u5b9a\u5e8f\u65bc\u5343\u79a7\u5e74\u521d\u5b8c\u6210\u5f8c\uff0c\u4f30\u8a08\u4eba\u7684\u67d3\u8272\u9ad4\u542b\u6709 2 \u842c\u591a\u7a2e\u57fa\u56e0\uff0c\u610f\u5373\u4eba\u985e\u7684\u86cb\u767d\u8cea\u7d04\u6709 2 \u842c\u9918\u7a2e\u3002\u9019 2 \u842c\u9918\u7a2e\u86cb\u767d\u8cea\u662f\u4e0d\u540c\u7684\uff0c\u4f46\u5177\u6709\u76f8\u540c\u7684\u7d44\u5408\u6210\u5206\uff1a\u80fa\u57fa\u9178\u3002\u7d55\u5927\u90e8\u5206\u7684\u86cb\u767d\u8cea\u90fd\u662f\u7531 20 \u7a2e\u5fc5\u9808\u80fa\u57fa\u9178\u4f9d\u7167\u4e0d\u540c\u7684\u5e8f\u5217\u8207\u7d44\u6210\u6bd4\u4f8b\u642d\u5efa\u3002<\/p>\n<p><strong>\u86cb\u767d\u8cea\u7684\u7d50\u69cb\u8207\u647a\u758a<\/strong><\/p>\n<p>\u86cb\u767d\u8cea\u7684\u5e8f\u5217\u9577\u5ea6\u4e0d\u4e00\uff0c\u77ed\u7684\u5982\u300c\u6cdb\u7d20\u300d\uff0876 \u9846\u80fa\u57fa\u9178\uff09\uff0c\u9577\u5247\u5982\u300c\u8102\u80aa\u9178\u5408\u6210\u9176\u300d\uff082511 \u9846\u80fa\u57fa\u9178\uff09\uff0c\u4f46\u5b83\u5011\u90fd\u7531\u5171\u540c\u7684\u80fa\u57fa\u9178\u55ae\u5143\u7d44\u5408\u800c\u6210\u3002\u80fa\u57fa\u9178\u7684\u5e8f\u5217\u7d44\u6210\u6703\u5f71\u97ff\u86cb\u767d\u8cea\u4e09\u7dad\u647a\u758a\u5916\u578b\uff0c\u4e5f\u8ddf\u529f\u80fd\u6709\u95dc\u3002\u9019\u4e9b\u7531\u300c\u80fa\u57fa\u9178\u5e8f\u5217\u300d\u5f15\u5c0e\u647a\u758a\u7684\u86cb\u767d\u8cea\u5728\u7d30\u80de\u5167\u3001\u8840\u7ba1\u4e2d\u3001\u76ae\u819a\u7b49\u8655\u90fd\u6709\u8457\u7279\u6b8a\u7684\u529f\u80fd\u3002\u8ca0\u8cac\u86cb\u767d\u8cea\u647a\u758a\u7684\u5730\u65b9\u4e5f\u5f88\u91cd\u8981\uff01\u86cb\u767d\u8cea\u7684\u80fa\u57fa\u9178\u5e8f\u5217\u5728\u4e00\u7a2e\u7a31\u70ba\u300c\u6838\u7cd6\u9ad4\uff08Ribosome\uff09\u300d\u7684\u5de8\u578b\u751f\u7269\u5408\u6210\u9176\u4e2d\u5373\u6642\u5f9e RNA \u8f49\u8b6f\uff0c\u4e26\u540c\u6642\u9032\u884c\u647a\u758a\uff08\u5716\u4e00\uff09\u3002<\/p>\n<p>\u7dad\u6301\u4e00\u500b\u7d30\u80de\u7684\u751f\u5b58\u9700\u8981\u5f88\u591a\u4e0d\u540c\u7684\u9175\u7d20\u88fd\u9020\u3001\u50ac\u5316\u4ee5\u53ca\u5206\u89e3\u80de\u5167\u7684\u7a2e\u7a2e\u5316\u5b78\u53cd\u61c9\u3002\u56e0\u6b64\u5f88\u591a\u86cb\u767d\u8cea\u90fd\u662f\u751f\u7269\u9176\uff0c\u8ca0\u8cac\u57f7\u884c\u4e0d\u540c\u7684\u529f\u80fd\uff0c\u8af8\u5982\u65b0\u751f\u80fa\u57fa\u9178\u5408\u6210\u3001\u6838\u9178\u55ae\u5143\u7684\u5408\u6210\u3001\u86cb\u767d\u8cea\u964d\u89e3\u3001\u7d30\u80de\u5167\u4ee3\u8b1d\u5c0f\u5206\u5b50\u7684\u5408\u6210\u8207\u6c34\u89e3\u7b49\uff0c\u90fd\u8ddf\u86cb\u767d\u8cea\u9176\u6709\u95dc\u3002\u86cb\u767d\u8cea\u7684\u4e09\u7dad\u9020\u578b\u6709\u5343\u5343\u767e\u767e\u7a2e\u4e0d\u540c\u3002\u9664\u64d4\u4efb\u751f\u7269\u9176\u7684\u529f\u80fd\u5916\uff0c\u6709\u90e8\u5206\u7684\u86cb\u767d\u8cea\u662f\u751f\u7269\u9aa8\u67b6\uff0c\u8ca0\u8cac\u642d\u67b6\u8d77\u7d30\u80de\u7684 3 \u5ea6\u7acb\u9ad4\u7a7a\u9593\u3002\u6709\u4e9b\u86cb\u767d\u8cea\u662f\u8ca0\u8cac\u8207\u4e0a\u4e0b\u6e38\u7684\u86cb\u767d\u8cea\u6e9d\u901a\uff0c\u64d4\u4efb\u8a0a\u865f\u50b3\u905e\u5206\u5b50\u3002\u6709\u4e9b\u86cb\u767d\u8cea\u5750\u843d\u5728\u7d30\u80de\u819c\u5167\uff0c\u64d4\u4efb\u50b3\u9001\u5316\u5b78\u6216\u751f\u7269\u5206\u5b50\u7684\u5411\u5916\u50b3\u9001\u6216\u5411\u5167\u904b\u88dc\u7684\u89d2\u8272\u3002<\/p>\n<p>\u86cb\u767d\u8cea\u88ab\u88fd\u9020\u5f8c\uff0c\u4e26\u975e\u6c38\u4e45\u5b58\u5728\u7d30\u80de\u5167\u3002\u7d30\u80de\u6709\u4e00\u500b\u56de\u6536\u5ee0\u7a31\u70ba\u86cb\u767d\u9176\u9ad4\uff08Proteasome\uff09\uff0c\u5c08\u9580\u8655\u7406\u300c\u7528\u4e0d\u5230\u300d\u3001\u300c\u647a\u758a\u932f\u8aa4\u300d\u7684\u86cb\u767d\u8cea\uff0c\u628a\u86cb\u767d\u8cea\u62c6\u89e3\u6210\u4e00\u500b\u500b\u7684\u80fa\u57fa\u9178\uff0c\u56de\u6536\u80fa\u57fa\u9178\u518d\u5229\u7528\u3002\u90a3\u86cb\u767d\u9176\u9ad4\u600e\u9ebc\u77e5\u9053\u54ea\u4e9b\u86cb\u767d\u8cea\u662f\u8981\u88ab\u300c\u8655\u7406\u300d\u7684\u5462\uff1f\u7d30\u80de\u5167\u86cb\u767d\u8cea\u6703\u88ab\u4e00\u500b\u7a31\u70ba\u300c\u6cdb\u7d20\uff08ubiquitin\uff09\u300d\u7684\u5c0f\u86cb\u767d\u8cea\u6240\u6a19\u8a18\uff0c\u5982\u540c\u6025\u96e3\u6551\u52a9\u73fe\u5834\u591a\u6aa2\u50b7\u5206\u985e\uff0c\u76ee\u524d\u5df2\u77e5\u6709\u591a\u7a2e\u6cdb\u7d20\u7684\u8a18\u865f\uff0c\u4e0d\u540c\u7684\u6cdb\u7d20\u8a18\u865f\u5f71\u97ff\u8457\u7d30\u80de\u5167\u7684\u751f\u7406\u529f\u80fd\u3002\u6bd4\u65b9\u8aaa\u6709\u8ca0\u8cac\u8a0a\u865f\u50b3\u905e\u7684 K63 \u9375\u7d50\uff0cDNA \u4fee\u5fa9\u7684 K11 \u6216 K29 \u9375\u7d50\u3002\u800c K48 \u9375\u7d50\u7248\u672c\u7684\u6cdb\u7d20\u93c8\u5247\u8ddf\u86cb\u767d\u9176\u9ad4\u9ad8\u5ea6\u76f8\u95dc\u3002\u5f85\u56de\u6536\u6216\u647a\u758a\u932f\u8aa4\u7684\u86cb\u767d\u8cea\u7d93\u904e K48 \u9375\u7d50\u7684\u6cdb\u7d20\u93c8\u6a19\u8a18\u5f8c\uff0c\u6703\u88ab\u5e36\u5f80\u86cb\u767d\u9176\u9ad4\u9032\u884c\u4e00\u7cfb\u5217\u7684\u964d\u89e3\u7a0b\u5e8f\uff08\u5716\u4e00\uff09\u3002<\/p>\n<div id=\"attachment_21652\" style=\"width: 1388px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-21652\" src=\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1.png\" alt=\"\u3010\u5c08\u6b04\u3011\u6dfa\u8ac7\u86cb\u767d\u8cea\u7684\u8a2d\u8a08\" width=\"1378\" height=\"808\" class=\"aligncenter size-full wp-image-32228\" srcset=\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1.png 1378w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1-300x176.png 300w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1-1024x600.png 1024w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1-768x450.png 768w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_1-1080x633.png 1080w\" sizes=\"(max-width: 1378px) 100vw, 1378px\" \/><p id=\"caption-attachment-21652\" class=\"wp-caption-text\">\u25b2\u5716\u4e00\uff1a(A)\u86cb\u767d\u8cea\u662f\u5f9e\u6838\u91a3\u9ad4\u5408\u6210\uff0c\u4e26\u7d93\u904e\u4e00\u7cfb\u5217\u7684\u647a\u758a\u904e\u7a0b\u800c\u7d44\u6210\u4e00\u500b\u86cb\u767d\u8cea\u7684\u7acb\u9ad4\u69cb\u578b\u3002\u86cb\u767d\u8cea\u6709\u5927\u6709\u5c0f\uff0c\u6709\u4e9b\u4e5f\u6703\u805a\u5408\u5f62\u6210\u4e00\u500b\u8907\u5408\u9ad4\u3002(B)\u647a\u758a\u6b63\u78ba\u6216\u662f\u932f\u8aa4\u7684\u86cb\u767d\u8cea\u6700\u7d42\u90fd\u6703\u7d93\u904e\u6cdb\u7d20\u7684\u6a19\u8a18\uff0c\u9001\u5f80\u86cb\u767d\u9176\u9ad4\u5206\u89e3\u3002<\/p><\/div>\n<p>&nbsp;<\/p>\n<p><strong>\u86cb\u767d\u8cea\u8a2d\u8a08\u5728\u6297\u75be\u75c5\u7684\u61c9\u7528\u2014\u2014\u4ee5\u6cdb\u7d20\u70ba\u4f8b<\/strong><\/p>\n<p>\u751f\u7269\u7cfb\u7d71\u8a2d\u8a08\u4e86\u6cdb\u7d20\u7576\u4f5c\u4e00\u7a2e\u7279\u6b8a\u6a19\u8a18\u7b26\u865f\u3002\u300c\u6a19\u8a18\u300d\u6cdb\u7d20\u7684\u662f\u5f88\u8907\u96dc\u7684\u4e09\u5c64\u6b21\u9023\u9396\u9175\u7d20\u53cd\u61c9\uff0c\u9996\u5148\u7531 E1 \u9175\u7d20\u555f\u52d5\u53cd\u61c9\uff0cE2 \u9175\u7d20\u8f49\u79fb\u6cdb\u7d20\uff0cE3 \u9175\u7d20\u628a\u6cdb\u7d20\u6a19\u8a18\u5230\u76ee\u6a19\u86cb\u767d\u8cea\u4e0a\u3002\u4eba\u985e\u57fa\u56e0\u7d44\u5171\u6709\u8d85\u904e 700 \u7a2e E1\u3001E2\u3001E3 \u9175\u7d20\u3002\u7576\u6a19\u8a18\u7684\u529f\u6548\u7d50\u675f\u5f8c\u5462\uff1f\u751f\u7269\u7cfb\u7d71\u4e5f\u8a2d\u8a08\u6709\u300c\u79fb\u9664\u300d\u6cdb\u7d20\u6a19\u8a18\uff08deubiquitylation\uff09\u529f\u80fd\u7684\u53bb\u6cdb\u7d20\u5316\u9176\u3002\u628a\u9644\u52a0\u7684\u6a19\u7c64\uff08\u6cdb\u7d20\uff09\u62ff\u6389\uff0c\u6062\u5fa9\u86cb\u767d\u8cea\u672c\u8eab\u7684\u529f\u80fd\u3002\u9019\u7a2e\u52d5\u614b\u7684\u80de\u5167\u6cdb\u7d20\u5e73\u8861\u6df1\u6df1\u7684\u5f71\u97ff\u7d30\u80de\u7684\u6b63\u5e38\u529f\u80fd\u3002<\/p>\n<p>\u591a\u5e74\u4f86\u79d1\u5b78\u5bb6\u5011\u5617\u8a66\u4f7f\u7528\u6cdb\u7d20\u5e8f\u5217\u8207\u69cb\u578b\u7576\u4f5c\u9aa8\u67b6\uff0c\u88fd\u9020\u51fa\u8b8a\u7a2e\u7248\u672c\u7684\u6cdb\u7d20 X\uff0c\u7528\u4ee5\u7af6\u722d\u80de\u5167\u6cdb\u7d20\u76f8\u9023\u7684\u9023\u9396\u9175\u7d20\u53cd\u61c9\uff0c\u9054\u5230\u6539\u8b8a\u7d30\u80de\u7684\u547d\u904b\u7684\u4f5c\u6cd5 <sup>2<\/sup>\u3002\u4ee5\u53bb\u6cdb\u7d20\u5316\u9176\u70ba\u4f8b\uff0c\u6cdb\u7d20\u93c8\u88ab\u53bb\u6cdb\u7d20\u5316\u9176\u6293\u4f4f\u4e26\u5207\u9664\uff0c\u91cb\u653e\u4e00\u500b\u4e00\u500b\u6cdb\u7d20\u56de\u5230\u7d30\u80de\u5167\u3002\u7576\u4fee\u6539\u7248\u7684\u6cdb\u7d20 X \u8ddf\u53bb\u6cdb\u7d20\u5316\u9176\u7684\u89aa\u548c\u529b\u512a\u5316\u4e0a\u5343\u500d\u5f8c\uff0c\u53bb\u6cdb\u7d20\u5316\u9176\u53ea\u6703\u88ab\u6cdb\u7d20 X \u7dca\u5bc6\u8457\u9ecf\u4f4f\uff0c\u7121\u6cd5\u6b63\u5e38\u57f7\u884c\u672c\u8eab\u7684\u529f\u80fd\uff0c\u7d30\u80de\u5167\u5927\u90e8\u5206\u7684\u6cdb\u7d20\u6a19\u8a18\u7684\u86cb\u767d\u8cea\u88ab\u63a5\u7e8c\u5730\u9001\u5230\u86cb\u767d\u9176\u9ad4\u9032\u884c\u964d\u89e3\uff0c\u53ef\u80fd\u52a0\u901f\u764c\u75c7\u7d30\u80de\u7684\u51cb\u96f6\u3002<\/p>\n<p>\u9019\u7a2e\u6cdb\u7d20\u7684\u5b9a\u5411\u6f14\u5316\uff08Directed Evolution\uff09\u5f80\u5f80\u9700\u8981\u7e41\u8907\u7684\u5be6\u9a57\u7be9\u9078\uff0c\u76f8\u7576\u8017\u6642\u3002\u8a66\u60f3\u82e5\u91dd\u5c0d\u6cdb\u7d20\u7684 10 \u500b\u4f4d\u9ede\uff08\u80fa\u57fa\u9178\uff09\u9032\u884c\u5b9a\u5411\u6f14\u5316\uff0c\u9700\u8981\u5f9e 20<sup>10<\/sup> \u7a2e\u7d44\u5408\u4e2d\u7be9\u9078\u5230\u9069\u5408 X 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&#8211; \u6cdb\u7d20\u300d\u5206\u5b50\u9593\u7684\u4e92\u52d5\u7db2\u7d61\uff0c\u5faa\u7406\u6027\u7684\u4fee\u6539\u6cdb\u7d20\uff0c\u4ee5\u6700\u5c11\u7684\u4fee\u6539\u9054\u5230\u6700\u597d\u7684\u6cdb\u7d20 X\uff08\u5716\u4e8c\uff09\u3002\u4ee5\u6b64\u6982\u5ff5\uff0c\u6211\u5011\u9078\u5b9a\u4e86\u4e2d\u6771\u56b4\u91cd\u547c\u5438\u75c7\u51a0\u72c0\u75c5\u6bd2\uff08MERS\uff09\u4e2d\u7684\u53bb\u6cdb\u7d20\u9176 PLpro \u4f5c\u70ba\u6280\u8853\u958b\u767c\u8207\u6982\u5ff5\u9a57\u8b49\u5e73\u53f0 <sup>3<\/sup>\u3002\u904e\u5f80\u4f7f\u7528\u566c\u83cc\u9ad4\u7be9\u9078\u6cd5\u627e\u5230\u7684\u6cdb\u7d20 X \u9700\u7a81\u8b8a 10-20 \u500b\u56fa\u5b9a\u4f4d\u9ede\uff0c\u7d93\u7531\u53cd\u8986\u7be9\u9078\u627e\u51fa\u4ff1\u9ad8\u89aa\u548c\u529b\u7684\u6cdb\u7d20\u8b8a\u7a2e\uff0c\u6b64\u6cdb\u7d20 X \u53ef\u6709\u6548\u6291\u5236 MERS \u75c5\u6bd2\u7684\u8907\u88fd\u6d3b\u6027\u3002\u4e0d\u540c\u65bc\u50b3\u7d71\u7684\u7be9\u9078\u6cd5\uff0c\u6211\u5011\u9996\u5148\u9451\u5b9a MERS PLpro \u8207\u6cdb\u7d20\u4e4b\u9593\u7684\u5206\u5b50\u4e92\u52d5\u7db2\u7d61\uff0c\u9078\u5b9a\u95dc\u9375\u7684\u4e92\u52d5\u4f4d\u9ede\uff0c\u9032\u884c\u6cdb\u7d20\u5e8f\u5217\u4fee\u6539\u8207\u4f7f\u7528\u96fb\u8166\u8a08\u7b97\u6a21\u64ec\u4e92\u52d5\u7db2\u7d61\u7684\u8b8a\u5316\u3002\u6700\u7d42\u53ea\u9700\u4fee\u6539 5 \u500b\u4f4d\u9ede\uff0c\u5c31\u53ef\u4ee5\u628a\u6cdb\u7d20\u8f49\u63db\u70ba\u6cdb\u7d20\uff38\uff08\u6587\u7ae0\u5167\u7a31\u70ba UbV5\uff09\uff0c\u6b64 UbV5 \u7684\u89aa\u548c\u529b\u662f\u6cdb\u7d20\u7684 2 \u842c 7,500 \u500d\uff0c\u6bd4\u8d77\u65e9\u5148\u7528\u566c\u83cc\u9ad4\u7be9\u9078\u7684\u7248\u672c\u512a\u5316\u66f4\u591a\u3002\u7576 UbV5 \u8207 MERS \u7684 PLpro \u53cd\u61c9\u5f8c\uff0c\u963b\u6b62 PLpro \u5207\u9664\u7d30\u80de\u5167\u7684\u6297\u75c5\u6bd2\u62b5\u79a6\u6a5f\u5236\uff0cPLpro \u7684\u6d3b\u6027\u8da8\u8fd1\u65bc\u96f6\uff0c\u75c5\u6bd2\u8907\u88fd\u4e5f\u6703\u505c\u6b62\u3002\u6b64 UbV5 \u6709\u6f5b\u529b\u4f5c\u70ba\u6297 MERS \u75c5\u6bd2\u7684\u5148\u9a45\u85e5\u7269\u3002\u540c\u6a23\u7684\u8a2d\u8a08\u65b9\u6cd5\u4e5f\u53ef\u61c9\u7528\u5230\u65b0\u51a0\u75c5\u6bd2\u8207\u591a\u7a2e\u75c5\u6bd2\u7cfb\u7d71\uff08\u5716\u4e8c\uff21\uff09\u3002<\/p>\n<p><strong>\u7121\u4e2d\u751f\u6709\u7684\u6cdb\u7d20 X<\/strong><\/p>\n<p>\u86cb\u767d\u8cea\u7684\u4e09\u7dad\u7d50\u69cb\u662f\u6839\u64da\u80fa\u57fa\u9178\u5e8f\u5217\u647a\u758a\u51fa\u4f86\u7684\uff0c\u8868\u793a\u6709\u6a5f\u6703\u5f9e\u80fa\u57fa\u9178\u5e8f\u5217\u7684\u7d44\u6210\u9810\u6e2c\u672a\u77e5\u86cb\u767d\u8cea\u7684\u4e09\u7dad\u7d50\u69cb\u3002\u591a\u5e74\u4f86\u79d1\u5b78\u5bb6\u52aa\u529b\u5728\u9810\u6e2c\u8207\u9a57\u8b49\u4e2d\u63a2\u7d22\u86cb\u767d\u8cea\u4e09\u7dad\u7d50\u69cb\uff0c\u7136\u800c\u9019\u500b\u9810\u6e2c\u7684\u8907\u96dc\u5ea6\u662f\u500b\u5929\u6587\u6578\u5b57\u3002\u4ee5\u6cdb\u7d20\u8209\u4f8b\uff0c\u958b\u982d\u7684\u7532\u786b\u80fa\u9178\uff08Methionine\uff09\u7dad\u6301\u4e0d\u8b8a\uff0c\u5f8c\u7e8c\u7684 75 \u9846\u4f4d\u9ede\u7686\u6709 20 \u7a2e\u8b8a\u5316\uff08\u56e0\u70ba\u6709 20 \u7a2e\u80fa\u57fa\u9178\uff09\uff0c\u7e3d\u5171\u6709 20<sup>75<\/sup> \u7a2e\u6392\u5217\u7d44\u5408\u3002\u7576\u96a8\u6a5f\u8b8a\u63db\u591a\u500b\u4f4d\u9ede\u7684\u80fa\u57fa\u9178\u5f8c\uff0c\u86cb\u767d\u8cea\u662f\u5426\u7dad\u6301\u4e00\u6a23\u7684\u4e09\u7dad\u7d50\u69cb\u5728\u904e\u53bb\u96e3\u4ee5\u6e96\u78ba\u9810\u6e2c\u3002\u8fd1\u5e74\u4f86\u7684\u4eba\u5de5\u667a\u6167\u8207\u6df1\u5ea6\u5b78\u7fd2\u8edf\u9ad4\u7684\u512a\u5316\uff0cDeepMind \u516c\u53f8\u63d0\u4f9b\u7684 AlphaFold \u8edf\u9ad4\u5927\u5e45\u5ea6\u7684\u63d0\u9ad8\u9810\u6e2c\u7684\u6e96\u78ba\u5ea6\uff0c\u4e26\u628a\u4eba\u985e\u4ee5\u53ca\u5176\u4ed6\u7269\u7a2e\u7684\u86cb\u767d\u8cea\u7d50\u69cb\u90fd\u9810\u6e2c\u4e00\u756a\uff0c\u76ee\u524d\u7d2f\u7a4d 48 \u500b\u7269\u7a2e\u7684\u86cb\u767d\u8cea\u8cc7\u6599\u5eab\u5171 2 \u5104\u500b\u7d50\u69cb\u514d\u8cbb\u958b\u653e <sup>4<\/sup>\u3002\u7d50\u5408\u897f\u96c5\u5716\u83ef\u76db\u9813\u5927\u5b78\u7684 Baker \u5be6\u9a57\u5ba4\u767c\u8868\u7684 ProteinMPNN \u86cb\u767d\u8cea\u5e8f\u5217\u512a\u5316\u8edf\u9ad4 <sup>5<\/sup>\uff0c\u6b64\u6642\u86cb\u767d\u8cea\u7684\u8a2d\u8a08\u8207\u9a57\u8b49\u53ef\u5168\u90e8\u4f7f\u7528\u96fb\u8166\u6a21\u64ec\u7684\u65b9\u5f0f\u9810\u5148\u7be9\u9078\uff0c\u7576\u8a08\u7b97\u8cc7\u6e90\u4e0d\u662f\u9650\u5236\u7684\u56e0\u7d20\u6642\uff0c\u7be9\u9078\u7684\u7d44\u5408\u53ef\u6bd4\u566c\u83cc\u9ad4\u7be9\u9078\u589e\u52a0\u6578\u767e\u842c\u500d\u3002<\/p>\n<p>\u4f9d\u6b64\u6982\u5ff5\uff0c\u6211\u5011\u63d0\u51fa\u4e00\u7c21\u6613\u7684\u8a2d\u8a08\u6d41\u7a0b\uff1a\u61c9\u7528 ProteinMPNN \u4fee\u6539\u6cdb\u7d20\u8207 Rsp5 E3 \u9176\u4e4b\u9593\u7684\u4e92\u52d5\u4f4d\u9ede\uff0c\u7528 AlphaFold \u9a57\u8b49 Rsp5 \u8207\u6cdb\u7d20 X \u7684\u7d50\u5408\uff0c\u518d\u6311\u9078\u6700\u5408\u7406\u7684 20 \u7a2e\u6cdb\u7d20 X \u5e8f\u5217\u9032\u884c\u5be6\u9a57\u9a57\u8b49\uff0c\u627e\u51fa\u9ad8\u6548\u7684\u6cdb\u7d20 X <sup>6<\/sup>\uff08\u5716\u4e8c\uff22\uff09\u3002\u4ee5\u7dad\u6301\u6cdb\u7d20\u4e09\u7dad\u69cb\u578b\u70ba\u524d\u63d0\uff0cProteinMPNN \u5927\u5e45\u5ea6\u7684\u4fee\u6539\u6cdb\u7d20\u7684\u5e8f\u5217\u7d44\u6210\uff0c\u4e0d\u540c\u65bc\u8a2d\u8a08 PLpro \u5c08\u5c6c\u7684\u6cdb\u7d20 X \u7b56\u7565\uff08\u7cbe\u6e96\u7a81\u8b8a\uff09\uff0c\u4fee\u6539\u904e\u534a\u7684\u5e8f\u5217\u4f4d\u9ede\u662f\u7a00\u9b06\u5e73\u5e38\u7684\u6578\u64da\u3002\u6211\u5011\u6aa2\u9a57\u6cdb\u7d20 X \u8207 Rsp5 \u7684\u4e92\u52d5\u89aa\u548c\u529b\u8b8a\u5316\uff0c\u8207\u6cdb\u7d20 X \u662f\u5426\u53ef\u6539\u8b8a Rsp5 E3 \u9176\u7684\u50ac\u5316\u80fd\u529b\u3002\u5728\u9019 20 \u500b\u5be6\u9a57\u7684\u7248\u672c\u4e2d\uff0c\u6709 5 \u500b\u89aa\u548c\u529b\u63d0\u9ad8\u3001\u50ac\u5316 Rsp5 \u6d3b\u6027\u4e5f\u589e\u52a0\u3002\u5176\u4e2d\u7de8\u865f R4 \u7684\u6cdb\u7d20 X \u53ef\u63d0\u5347\u89aa\u548c\u529b\u7d04 25 \u500d\uff0c\u5f37\u5316 Rsp5 E3 \u9176\u7684\u6d3b\u6027 6 \u500d\u4ee5\u4e0a\u3002R4 \u7684\u86cb\u767d\u8cea\u6676\u9ad4\u7d50\u69cb\u4e5f\u8207\u6cdb\u7d20\u6beb\u7121\u5dee\u7570\uff0c\u9019\u662f\u5f88\u4ee4\u4eba\u6fc0\u596e\u7684\u6210\u679c\u300220 \u500b\u5be6\u8b49\u4e2d\u6709 5 \u500b\u6cdb\u7d20 X \u5c0d Rsp5 \u6709\u5f71\u97ff\u529b\uff0c25% \u7684\u6210\u529f\u7387\u770b\u4f3c\u4e0d\u9ad8\uff0c\u5be6\u5247\u6548\u7387\u5947\u9ad8\u3002\u7121\u9700\u4eba\u529b\u5206\u6790\u3001\u7121\u9700\u5efa\u69cb\u7be9\u9078\u5e73\u53f0\u3001\u96fb\u8166\u6a21\u64ec\u904b\u7b97\u901f\u7387\u65e5\u6f38\u52a0\u901f\u7b49\u512a\u52e2\uff0c\u7d04\u7565 5-10 \u5929\u53ef\u5b8c\u6210\u521d\u6b65\u7be9\u9078\u3002<\/p>\n<div id=\"attachment_21652\" style=\"width: 1387px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-21652\" src=\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2.png\" alt=\"\u3010\u5c08\u6b04\u3011\u6dfa\u8ac7\u86cb\u767d\u8cea\u7684\u8a2d\u8a08\" width=\"1377\" height=\"835\" class=\"aligncenter size-full wp-image-32229\" srcset=\"https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2.png 1377w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2-300x182.png 300w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2-1024x621.png 1024w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2-768x466.png 768w, https:\/newsletter.sinica.edu.tw\/wp-content\/uploads\/2023\/08\/3-1_2-1080x655.png 1080w\" sizes=\"(max-width: 1377px) 100vw, 1377px\" \/><p id=\"caption-attachment-21652\" class=\"wp-caption-text\">\u25b2\u5716\u4e8c\uff1a\u5169\u7a2e\u86cb\u767d\u8cea\u8a2d\u8a08\u6848\u4f8b\u4ecb\u7d39\u3002(A)\u63a1\u7528\u5faa\u7406\u6027\u8a2d\u8a08\u6cd5\uff0c\u9451\u5b9a\u5169\u7a2e\u86cb\u767d\u8cea\u4e4b\u9593\u7684\u4e92\u52d5\u7db2\u7d61\uff0c\u512a\u5316\u80fa\u57fa\u9178\u7a2e\u985e\uff0c\u7522\u751f\u65b0\u7684\u5e8f\u5217\u3002<br \/>\n(B)\u4f7f\u7528\u4eba\u5de5\u667a\u6167\u8edf\u9ad4\u81ea\u52d5\u5206\u6790\u8207\u751f\u6210\u65b0\u7684\u86cb\u767d\u8cea\u5e8f\u5217\u3002<\/p><\/div>\n<p>&nbsp;<\/p>\n<p>\u9019\u7a2e\u65b0\u7a4e\u7684\u86cb\u767d\u8cea\u8a2d\u8a08\u6cd5\uff0c\u5c07\u9010\u6b65\u53d6\u4ee3\u7684\u96a8\u6a5f\u7a81\u8b8a\u5b9a\u5411\u6f14\u5316\u6cd5\uff0c\u5e8f\u5217\u4fee\u6539\u904e\u7684\u86cb\u767d\u8cea\uff0c\u5728\u751f\u6280\u3001\u91ab\u85e5\u9818\u57df\u7684\u61c9\u7528\u66f4\u662f\u6f5b\u529b\u7121\u7aae\u3002<\/p>\n<p>&nbsp;<\/p>\n<hr>\n<ol>\n<li>Berzelius \u63d0\u51fa\u300c\u50ac\u5316 catalysis\u300d\uff0c\u300c\u805a\u5408\u7269 polymer\u300d\uff0c\u300c\u7570\u69cb\u7269 isomer\u300d\u7b49\u91cd\u8981\u5316\u5b78\u8853\u8a9e\uff0c\u4ed6\u4e5f\u88ab\u5c0a\u70ba\u745e\u5178\u5316\u5b78\u4e4b\u7236\u3002<\/li>\n<li>Ernst, A.; et al., A strategy for modulation of enzymes in the ubiquitin system. Science 2013, 339 (6119), 590-5. <a href=\"https:\/www.science.org\/doi\/10.1126\/science.1230161\" rel=\"noopener\" target=\"_blank\">https:\/www.science.org\/doi\/10.1126\/science.1230161<\/a><\/li>\n<li>Hung TI, Hsieh Y-J, Lu W-L, Wu K-P, Chang CA,\u201cWhat Strengthens Protein-Protein Interactions: Analysis and Applications of Residue Correlation Networks.\u201dBioRxiv preprint. <a href=\"https:\/doi.org\/10.1101\/2023.03.15.532709\" rel=\"noopener\" target=\"_blank\">https:\/doi.org\/10.1101\/2023.03.15.532709<\/a><\/li>\n<li><a href=\"https:\/alphafold.ebi.ac.uk\" rel=\"noopener\" target=\"_blank\">https:\/alphafold.ebi.ac.uk<\/a><\/li>\n<li>Dauparas, J.; et al., Robust deep learning-based protein sequence design using ProteinMPNN. Science 2022, 378 (6615), 49-56. <a href=\"https:\/www.science.org\/doi\/10.1126\/science.add2187\" rel=\"noopener\" target=\"_blank\">https:\/www.science.org\/doi\/10.1126\/science.add2187<\/a> Source code: <a href=\"https:\/github.com\/dauparas\/ProteinMPNN\" rel=\"noopener\" target=\"_blank\">https:\/github.com\/dauparas\/ProteinMPNN<\/a><\/li>\n<li>Kao H-W; et. al. Robust design of effective allosteric activators for Rsp5 E3 ligase using the machine-learning tool ProteinMPNN ACS synthetic biology 2023, online pub first, <a href=\"https:\/doi.org\/10.1021\/acssynbio.3c00042\" rel=\"noopener\" target=\"_blank\">https:\/doi.org\/10.1021\/acssynbio.3c00042<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>\u86cb\u767d\u8cea\u662f\u4ec0\u9ebc\uff1f\u80fd\u5403\u55ce\uff1f\u86cb\u767d\u8cea\uff0c\u662f\u4e00\u7a2e\u751f\u7269\u5de8\u5206\u5b50\u3002\u86cb\u767d\u8cea\u662f\u751f\u7269\u8cf4\u4ee5\u7dad\u751f\u7684\u91cd\u8981\u7269\u8cea\uff0c\u5176\u82f1\u6587\u300cprotein\u300d\u662f 19 \u4e16\u7d00\u745e\u5178\u5316\u5b78\u5bb6 J\u00f6ns Jacob Berzelius \u6240\u767c\u660e\u7684 <sup>1<\/sup>\u3002 Berzelius \u6839\u64da\u8377\u862d\u79d1\u5b78\u5bb6 Gerardus Johannes Mulder \u5206\u6790\u86cb\u767d\u8cea\u7684\u7d44\u6210\u662f\u7531\u78b3\u3001\u6c2b\u3001\u6c27\u3001\u6c2e\u3001\u786b\u8207\u78f7\u7684\u5171\u540c\u7d44\u5408\uff0c\u4e26\u4ee5\u5e0c\u81d8\u5b57\u300c\u03c0\u03c1\u03ce\u03c4\u03b5\u03b9\u03bf\u03c2\uff08proteios\uff09\u300d\u70ba\u5b57\u6e90\uff0c\u610f\u5373\u4e3b\u8981\uff08primary\uff09\uff0c\u5b9a\u7fa9\u70ba\u300cprotein\u300d\u3002<\/p>\n","protected":false},"author":1,"featured_media":32283,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[991,983],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/32225"}],"collection":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/comments?post=32225"}],"version-history":[{"count":1,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/32225\/revisions"}],"predecessor-version":[{"id":32282,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/32225\/revisions\/32282"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/media\/32283"}],"wp:attachment":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/media?parent=32225"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/categories?post=32225"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/tags?post=32225"}],"curies":[{"name":"wp","href":"https:\/api.w.org\/{rel}","templated":true}]}}