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Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling

Item Type:Article
Title:Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling
Creators Name:Daumke, O. and Lundmark, R. and Vallis, Y. and Martens, S. and Butler, P.J.G. and McMahon, H.T.
Abstract:The ability to actively remodel membranes in response to nucleotide hydrolysis has largely been attributed to GTPases of the dynamin superfamily, and these have been extensively studied1. Epsin homology (EH)-domain-containing proteins (EHDs/RME-1/pincher) comprise a less-well-characterized class of highly conserved eukaryotic ATPases implicated in clathrin-independent endocytosis2, and recycling from endosomes3, 4. Here we show that EHDs share many common features with the dynamin superfamily, such as a low affinity for nucleotides, the ability to tubulate liposomes in vitro, oligomerization around lipid tubules in ring-like structures and stimulated nucleotide hydrolysis in response to lipid binding. We present the structure of EHD2, bound to a non-hydrolysable ATP analogue, and provide evidence consistent with a role for EHDs in nucleotide-dependent membrane remodelling in vivo. The nucleotide-binding domain is involved in dimerization, which creates a highly curved membrane-binding region in the dimer. Oligomerization of dimers occurs on another interface of the nucleotide-binding domain, and this allows us to model the EHD oligomer. We discuss the functional implications of the EHD2 structure for understanding membrane deformation.
Keywords:Molecular Graphics, Protein Structures, Mammalian Cells, C-Elegans, Dynamin, Domain, Refinement, Program, RME-1, Association
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:449
Number:7164
Page Range:923-927
Date:3 October 2007
Official Publication:https://doi.org/10.1038/nature06173
PubMed:View item in PubMed

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