Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation.
Members of the Bin/amphiphysin/Rvs (BAR) domain protein superfamily are involved in membrane remodeling in various cellular pathways ranging from endocytic vesicle and T-tubule formation to cell migration and neuromorphogenesis. Membrane curvature induction and stabilization are encoded within the BAR or Fer-CIP4 homology-BAR (F-BAR) domains, alpha-helical coiled coils that dimerize into membrane-binding modules. BAR/F-BAR domain proteins often contain an SH3 domain, which recruits binding partners such as the oligomeric membrane-fissioning GTPase dynamin. How precisely BAR/F-BAR domain-mediated membrane deformation is regulated at the cellular level is unknown. Here we present the crystal structures of full-length syndapin 1 and its F-BAR domain. Our data show that syndapin 1 F-BAR-mediated membrane deformation is subject to autoinhibition by its SH3 domain. Release from the clamped conformation is driven by association of syndapin 1 SH3 with the proline-rich domain of dynamin 1, thereby unlocking its potent membrane-bending activity. We hypothesize that this mechanism might be commonly used to regulate BAR/F-BAR domain-induced membrane deformation and to potentially couple this process to dynamin-mediated fission. Our data thus suggest a structure-based model for SH3-mediated regulation of BAR/F-BAR domain function.
Rao
Yijian
Y
Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Ma
Qingjun
Q
Vahedi-Faridi
Ardeschir
A
Sundborger
Anna
A
Pechstein
Arndt
A
Puchkov
Dmytro
D
Luo
Lin
L
Shupliakov
Oleg
O
Saenger
Wolfram
W
Haucke
Volker
V
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D018909:src Homology Domains
D002352:Carrier Proteins
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