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

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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., Lürick, A., Kuhlee, A., Kleine Balderhaar, H., Bröcker, C., Kümmel, D., Engelbrecht-Vandré, S., Gohlke, U., Raunser, S., 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
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

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