Article
- The EMBO Journal (2006) 25, 2898 - 2910
- doi:10.1038/sj.emboj.7601174
Published online: 8 June 2006
Subject Categories:
Mechanism of endophilin N-BAR domain-mediated membrane curvature
Jennifer L Gallop1,ab, Christine C Jao2,a, Helen M Kent1, P Jonathan G Butler1, Philip R Evans1, Ralf Langen2 and Harvey T McMahon1
- MRC Laboratory of Molecular Biology, Cambridge, UK
- Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA
Correspondence to:
Harvey T McMahon, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402311; Fax: +44 1223 402310; E-mail: hmm@mrc-lmb.cam.ac.uk
Ralf Langen, Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, University of Southern California, 1501 San Pablo Street, Los Angeles, CA 90033, USA. E-mail: langen@usc.edu
Philip R Evans, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. E-mail: pre@mrc-lmb.cam.ac.uk
aThese authors contributed equally to this work
bPresent address: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Received 5 April 2006; Accepted 8 May 2006
Abstract
Endophilin-A1 is a BAR domain-containing protein enriched at synapses and is implicated in synaptic vesicle endocytosis. It binds to dynamin and synaptojanin via a C-terminal SH3 domain. We examine the mechanism by which the BAR domain and an N-terminal amphipathic helix, which folds upon membrane binding, work as a functional unit (the N-BAR domain) to promote dimerisation and membrane curvature generation. By electron paramagnetic resonance spectroscopy, we show that this amphipathic helix is peripherally bound in the plane of the membrane, with the midpoint of insertion aligned with the phosphate level of headgroups. This places the helix in an optimal position to effect membrane curvature generation. We solved the crystal structure of rat endophilin-A1 BAR domain and examined a distinctive insert protruding from the membrane interaction face. This insert is predicted to form an additional amphipathic helix and is important for curvature generation. Its presence defines an endophilin/nadrin subclass of BAR domains. We propose that N-BAR domains function as low-affinity dimers regulating binding partner recruitment to areas of high membrane curvature.
Keywords:
- amphiphysin,
- clathrin-mediated endocytosis,
- dynamin,
- endophilin,
- kiss-and-run,
- nadrin/RICH
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
The BAR-domain family of proteins: a case of bending and binding?
EMBO reports Review (01 Mar 2004)
NEWS AND VIEWS
Membrane transport The making of a vesicle
Nature News and Views (26 Sep 2002)
Cell biology Lipid membranes shape up
Nature News and Views (09 Sep 1999)
RESEARCH
Pore dilation of neuronal P2X receptor channels
Nature Neuroscience Article (01 Apr 1999)
Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms
The EMBO Journal Article (21 Jun 2006)
