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Elife. 2017 Sep 19;6. pii: e27396. doi: 10.7554/eLife.27396.

Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo.

Author information

1
Department of Biochemistry, University of Washington School of Medicine, Seattle, United States.
2
Department of Biology, California State University, San Bernardino, United States.
3
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States.
4
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, United States.

Abstract

Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here, we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, Vps33/HOPS promotes productive SNARE assembly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially zipped, Sec17 promotes fusion in either the presence or absence of HOPS, but with faster kinetics when HOPS is absent, suggesting that ejection of the SM is a rate-limiting step.

KEYWORDS:

AP-3; HOPS; Rab; S. cerevisiae; Sec1/Munc18; Vps33; biochemistry; cell biology; lysosome

PMID:
28925353
PMCID:
PMC5643095
DOI:
10.7554/eLife.27396
[Indexed for MEDLINE]
Free PMC Article

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