{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:49:56Z","timestamp":1789361396576,"version":"build-2803163510"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,26]]},"abstract":"<jats:p>\n                    RING domains act in a variety of unrelated biochemical reactions, with many of these domains forming key parts of supramolecular assemblies in cells. Here, we observe that purified RINGs from a variety of functionally unrelated proteins, including promyelocytic leukemia protein, KAP-1\/TIF1\u03b2, Z, Mel18, breast cancer susceptibility gene product 1 (BRCA1), and BRCA1-associated RING domain (BARD1), self-assemble into supramolecular structures\n                    <jats:italic>in vitro<\/jats:italic>\n                    that resemble those they form in cells. RING bodies form polyvalent binding surfaces and scaffold multiple partner proteins. Separation of RING bodies from monomers reveals that self-assembly controls and amplifies their specific activities in two unrelated biochemistries: reduction of 5\u2032 mRNA cap affinity of eIF4E by promyelocytic leukemia protein and Z, and E3 ubiquitin conjugation activity of BARD1:BRCA1. Functional significance of self-assembly is underscored by partial restoration of assembly and E3 activity of cancer predisposing BRCA1 mutant by forced oligomerization. RING self-assembly creates bodies that act structurally as polyvalent scaffolds, thermodynamically by amplifying activities of partner proteins, and catalytically by spatiotemporal coupling of enzymatic reactions. These studies reveal a general paradigm of how supramolecular structures may function in cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.202608799","type":"journal-article","created":{"date-parts":[[2002,11,26]],"date-time":"2002-11-26T12:42:52Z","timestamp":1038314572000},"page":"15404-15409","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Control of biochemical reactions through supramolecular RING domain self-assembly"],"prefix":"10.1073","volume":"99","author":[{"given":"Alex","family":"Kentsis","sequence":"first","affiliation":[{"name":"Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald E.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L. B.","family":"Borden","sequence":"additional","affiliation":[{"name":"Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,11,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.10.3167.410k44_3167_3215"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5237.789"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389203003381478"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(96)80017-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3402"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000881200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012317299"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.5.3819-3826.1998"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1001-833"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201252200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.5170"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07139.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010663200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00254.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.12075"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.7.3293-3300.2000"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4239"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.16.4547"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/35056563"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00057-X"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.503"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5443.1321"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1927"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106551200"},{"key":"e_1_3_3_26_2","unstructured":"Wyman J. & Gill S. 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(1990) Binding and Linkage: Functional Chemistry of Biological Macromolecules (University Science Books Mill Valley CA)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(01)00269-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.202608799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T20:56:14Z","timestamp":1650920174000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.202608799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11,18]]},"references-count":27,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2002,11,26]]}},"alternative-id":["10.1073\/pnas.202608799"],"URL":"https:\/\/doi.org\/10.1073\/pnas.202608799","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11,18]]},"assertion":[{"value":"2002-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-10-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}