title: Structural basis of membrane invagination by F-BAR domains.
abstract: BAR superfamily domains shape membranes through poorly understood mechanisms. We solved structures of F-BAR modules bound to flat and curved bilayers using electron (cryo)microscopy. We show that membrane tubules form when F-BARs polymerize into helical coats that are held together by lateral and tip-to-tip interactions. On gel-state membranes or after mutation of residues along the lateral interaction surface, F-BARs adsorb onto bilayers via surfaces other than their concave face. We conclude that membrane binding is separable from membrane bending, and that imposition of the module's concave surface forces fluid-phase bilayers to bend locally. Furthermore, exposure of the domain's lateral interaction surface through a change in orientation serves as the crucial trigger for assembly of the helical coat and propagation of bilayer bending. The geometric constraints and sequential assembly of the helical lattice explain how F-BAR and classical BAR domains segregate into distinct microdomains, and provide insight into the spatial regulation of membrane invagination.
authors.affiliation: Departments of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Frost
authors.forename: Rushika
authors.initials: R
authors.lastname: Perera
authors.forename: Aurélien
authors.initials: A
authors.lastname: Roux
authors.forename: Krasimir
authors.initials: K
authors.lastname: Spasov
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Vinzenz M
authors.initials: VM
authors.lastname: Unger
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D020285:Cryoelectron Microscopy; D034281:Dynamins / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C433770:FNBP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008081:Liposomes; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human; D049452:Green Fluorescent Proteins; D034281:Dynamins