{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T22:34:42Z","timestamp":1770503682789,"version":"3.49.0"},"reference-count":63,"publisher":"American Society for Cell Biology (ASCB)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>The fusion of yeast vacuoles, like other organelles, requires a Rab-family guanosine triphosphatase (Ypt7p), a Rab effector and Sec1\/Munc18 (SM) complex termed HOPS (homotypic fusion and vacuole protein sorting), and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The central 0-layer of the four bundled vacuolar SNAREs requires the wild-type three glutaminyl (Q) and one arginyl (R) residues for optimal fusion. Alterations of this layer dramatically increase the K<jats:sub>m<\/jats:sub>value for SNAREs to assemble trans-SNARE complexes and to fuse. We now find that added purified HOPS complex strongly suppresses the fusion of vacuoles bearing 0-layer alterations, but it has little effect on the fusion of vacuoles with wild-type SNAREs. HOPS proofreads at two levels, inhibiting the formation of trans-SNARE complexes with altered 0-layers and suppressing the ability of these mismatched 0-layer trans-SNARE complexes to support membrane fusion. HOPS proofreading also extends to other parts of the SNARE complex, because it suppresses the fusion of trans-SNARE complexes formed without the N-terminal Phox homology domain of Vam7p (Q<jats:sub>c<\/jats:sub>). Unlike some other SM proteins, HOPS proofreading does not require the Vam3p (Q<jats:sub>a<\/jats:sub>) N-terminal domain. HOPS thus proofreads SNARE domain and N-terminal domain structures and regulates the fusion capacity of trans-SNARE complexes, only allowing full function for wild-type SNARE configurations. This is the most direct evidence to date that HOPS is directly involved in the fusion event.<\/jats:p>","DOI":"10.1091\/mbc.e08-01-0077","type":"journal-article","created":{"date-parts":[[2008,4,3]],"date-time":"2008-04-03T01:55:07Z","timestamp":1207187707000},"page":"2500-2508","source":"Crossref","is-referenced-by-count":105,"title":["HOPS Proofreads the<i>trans<\/i>-SNARE Complex for Yeast Vacuole Fusion"],"prefix":"10.1091","volume":"19","author":[{"given":"Vincent J.","family":"Starai","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755"}]},{"given":"Christopher M.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755"}]},{"given":"William","family":"Wickner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1038\/sj.emboj.7601820","volume":"26","author":"Bethani I.","year":"2007","journal-title":"EMBO J"},{"key":"B2","doi-asserted-by":"crossref","first-page":"R255","DOI":"10.1016\/j.cub.2007.02.006","volume":"17","author":"Burgoyne R. 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