Structural basis of Vps33A recruitment to the human HOPS complex by Vps16
- 30 July 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (33), 13345-13350
- https://doi.org/10.1073/pnas.1307074110
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.This publication has 52 references indexed in Scilit:
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