title: A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion.
abstract: Yeast vacuoles undergo priming, docking, and homotypic fusion, although little has been known of the connections between these reactions. Vacuole-associated Vam2p and Vam6p (Vam2/6p) are components of a 65S complex containing SNARE proteins. Upon priming by Sec18p/NSF and ATP, Vam2/6p is released as a 38S subcomplex that binds Ypt7p to initiate docking. We now report that the 38S complex consists of both Vam2/6p and the class C Vps proteins [Reider, S. E. and Emr, S. D. (1997) Mol. Biol. Cell 8, 2307-2327]. This complex includes Vps33p, a member of the Sec1 family of proteins that bind t-SNAREs. We term this 38S complex HOPS, for homotypic fusion and vacuole protein sorting. This unexpected finding explains how Vam2/6p associates with SNAREs and provides a mechanistic link of the class C Vps proteins to Ypt/Rab action. HOPS initially associates with vacuole SNAREs in "cis" and, after release by priming, hops to Ypt7p, activating this Ypt/Rab switch to initiate docking.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755-3844, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Seals
authors.forename: G
authors.initials: G
authors.lastname: Eitzen
authors.forename: N
authors.initials: N
authors.lastname: Margolis
authors.forename: W T
authors.initials: WT
authors.lastname: Wickner
authors.forename: A
authors.initials: A
authors.lastname: Price
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000145:classification / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D005656:Fungal Proteins / Q000145:classification / Q000378:metabolism*; D046911:Macromolecular Substances; D008561:Membrane Fusion / Q000187:drug effects; D008565:Membrane Proteins / Q000145:classification / Q000378:metabolism; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000145:classification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014617:Vacuoles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000906:Antibodies; D002352:Carrier Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; C077734:NPL3 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C406817:VAM6 protein, S cerevisiae; C065454:VPS33 protein, S cerevisiae; C083878:VPS41 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C079005:YPT7 protein, S cerevisiae; D020691:rab GTP-Binding Proteins