1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
2. These authors contributed equally to this work.
3. Present addresses: Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Str. 10, 13092 Berlin, Germany (O.D.); Umeå University, Department of Medical Biochemistry and Biophysics, 90187 Umeå, Sweden (R.L.).

Correspondence to: Oliver Daumke^1,2,3Harvey T. McMahon¹ Correspondence and requests for materials should be addressed to H.T.McM. (Email: hmm@mrc-lmb.cam.ac.uk) or O.D. (Email: oliver.daumke@mdc-berlin.de).

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. Eps15 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 endosomes^{3, 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.

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