A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion

Yeast vacuoles undergo priming, docking, and homotypic fusion, although lit tle has been known of the connections between these reactions. Vacuole-asso ciated 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 [Reid er, S. E. and Emr, S. D. (1997) Mel. Biol. Cell 8, 2307-2327]. This complex includes Vps33p, a member of the Sec1 family of proteins that bind t-SNARE s. We term this 385 complex HOPS, for homotypic fusion and vacuole protein sorting. This unexpected finding explains how Vam2/6p associates with SNARE s and provides a mechanistic link of the class C Vps proteins to Ypt/Rab ac tion. HOPS initially associates with vacuole SNAREs in "cis" and, after rel ease by priming, hops to Ypt7p, activating this Ypt/Rab switch to initiate docking.