title: Structural basis of membrane bending by the N-BAR protein endophilin.
abstract: Functioning as key players in cellular regulation of membrane curvature, BAR domain proteins bend bilayers and recruit interaction partners through poorly understood mechanisms. Using electron cryomicroscopy, we present reconstructions of full-length endophilin and its N-terminal N-BAR domain in their membrane-bound state. Endophilin lattices expose large areas of membrane surface and are held together by promiscuous interactions between endophilin's amphipathic N-terminal helices. Coarse-grained molecular dynamics simulations reveal that endophilin lattices are highly dynamic and that the N-terminal helices are required for formation of a stable and regular scaffold. Furthermore, endophilin accommodates different curvatures through a quantized addition or removal of endophilin dimers, which in some cases causes dimerization of endophilin's SH3 domains, suggesting that the spatial presentation of SH3 domains, rather than affinity, governs the recruitment of downstream interaction partners.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, 2205 Campus Drive, Evanston, IL 60208, USA.
authors.forename: Carsten
authors.initials: C
authors.lastname: Mim
authors.forename: Haosheng
authors.initials: H
authors.lastname: Cui
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gawronski-Salerno
authors.forename: Adam
authors.initials: A
authors.lastname: Frost
authors.forename: Edward
authors.initials: E
authors.lastname: Lyman
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
authors.forename: Vinzenz M
authors.initials: VM
authors.lastname: Unger
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D009419:Nerve Tissue Proteins; C075637:amphiphysin; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase