Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Structural identification of the VPS18 β-propeller reveals a critical role in the HOPS complex stability and function

[img]
Preview
PDF (Original article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB

Item Type:Article
Title:Structural identification of the VPS18 β-propeller reveals a critical role in the HOPS complex stability and function
Creators Name:Behrmann, H. and Lürick, A. and Kuhlee, A. and Kleine Balderhaar, H. and Bröcker, C. and Kümmel, D. and Engelbrecht-Vandré, S. and Gohlke, U. and Raunser, S. and Heinemann, U. and Ungermann, C.
Abstract:Membrane fusion at the vacuole, the lysosome equivalent in yeast, requires the HOPS tethering complex, which is recruited by the Rab7 GTPase Ypt7. HOPS provides a template for the assembly of SNAREs and thus likely confers fusion at a distinct position on vacuoles. Five of the six subunits in HOPS have a similar domain prediction with strong similarity to COPII subunits and nuclear porins. Here, we show that Vps18 indeed has a 7-bladed {beta}-propeller as its N-terminal domain by revealing its structure at 2.14 Angstroem. The Vps18 N-terminal domain can interact with the N-terminal part of Vps11 and also binds to lipids. Although deletion of the Vps18 N-terminal domain does not preclude HOPS assembly, as revealed by negative stain electron microscopy, the complex is instable and cannot support membrane fusion in vitro. We thus conclude that the {beta}-propeller of Vps18 is required for HOPS stability and function, and that it can serve as a starting point for further structural analyses of the HOPS tethering complex.
Keywords:Crystal Structure, Endosome, Membrane Fusion, Rab, SNARE Proteins, HOPS, Tethering Complex, Vacuole
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:289
Number:48
Page Range:33503-33512
Date:28 November 2014
Official Publication:https://doi.org/10.1074/jbc.M114.602714
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library