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Structural basis of Vps33A recruitment to the human HOPS complex by Vps16.

ABSTRACT: The multisubunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for late endosome-lysosome and autophagosome-lysosome fusion in mammals. We have determined the crystal structure of the human HOPS subunit Vps33A, confirming its identity as a Sec1/Munc18 family member. We show that HOPS subunit Vps16 recruits Vps33A to the human HOPS complex and that residues 642-736 are necessary and sufficient for this interaction, and we present the crystal structure of Vps33A in complex with Vps16(642-736). Mutations at the binding interface disrupt the Vps33A-Vps16 interaction both in vitro and in cells, preventing recruitment of Vps33A to the HOPS complex. The Vps33A-Vps16 complex provides a structural framework for studying the association between Sec1/Munc18 proteins and tethering complexes.

SUBMITTER: Graham SC

PROVIDER: S-EPMC3746937 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Structural basis of Vps33A recruitment to the human HOPS complex by Vps16.

Graham Stephen C SC Wartosch Lena L Gray Sally R SR Scourfield Edward J EJ Deane Janet E JE Luzio J Paul JP Owen David J DJ

Proceedings of the National Academy of Sciences of the United States of America 20130730 33

The multisubunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for late endosome-lysosome and autophagosome-lysosome fusion in mammals. We have determined the crystal structure of the human HOPS subunit Vps33A, confirming its identity as a Sec1/Munc18 family member. We show that HOPS subunit Vps16 recruits Vps33A to the human HOPS complex and that residues 642-736 are necessary and sufficient for this interaction, and we present the crystal structure ...[more]

PMID: 23901104

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Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes.

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