title: Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms.
abstract: The crescent-shaped BAR (Bin/Amphiphysin/Rvs-homology) domain dimer is a versatile protein module that senses and generates positive membrane curvature. The BAR domain dimer of human endophilin-A1, solved at 3.1 A, has a unique structure consisting of a pair of helix-loop appendages sprouting out from the crescent. The appendage's short helices form a hydrophobic ridge, which runs across the concave surface at its center. Examining liposome binding and tubulation in vitro using purified BAR domain and its mutants indicated that the ridge penetrates into the membrane bilayer and enhances liposome tubulation. BAR domain-expressing cells exhibited marked plasma membrane tubulation in vivo. Furthermore, a swinging-arm mutant lost liposome tubulation activity yet retaining liposome binding. These data suggested that the rigid crescent dimer shape is crucial for the tubulation. We here propose that the BAR domain drives membrane curvature by coordinate action of the crescent's scaffold mechanism and the ridge's membrane insertion in addition to membrane binding via amino-terminal amphipathic helix.
authors.affiliation: Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Masuda
authors.forename: Soichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Manami
authors.initials: M
authors.lastname: Sone
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohki
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamioka
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D041681:NIH 3T3 Cells; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008081:Liposomes; C107640:SH3GL2 protein, human; D014364:Tryptophan