Structural identification of the VPS18 β-propeller reveals a critical role in the HOPS complex stability and function
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 |
---|
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 per month over past year
|