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

被引：77

作者：

Graham, Stephen C. ^{[1
,3
]}

Wartosch, Lena ^{[1
]}

Gray, Sally R. ^{[1
]}

Scourfield, Edward J. ^{[3
]}

Deane, Janet E. ^{[2
]}

Luzio, J. Paul ^{[1
]}

Owen, David J. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Clin Biochem, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[2] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[3] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 33期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

DEPENDENT MEMBRANE-FUSION; SM PROTEIN; SNARE COMPLEX; TETHERING COMPLEXES; RENAL DYSFUNCTION; RAB INTERACTIONS; N-PEPTIDE; BINDING; DOMAIN; TRAFFICKING;

D O I：

10.1073/pnas.1307074110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：13345 / 13350

页数：6

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