Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 18; pp. 8213 - 8218
• Main Authors: Rao, Yijian, Ma, Qingjun, Vahedi-Faridi, Ardeschir, Sundborger, Anna, Pechstein, Arndt, Puchkov, Dmytro, Luo, Lin, Shupliakov, Oleg, Saenger, Wolfram, Haucke, Volker
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.05.2010; National Acad Sciences
• Subjects: Amino Acid Sequence; Animals; Bending; Binding sites; Biological Sciences; Carrier Proteins - chemistry; Carrier Proteins - ultrastructure; Cell adhesion & migration; Cell Membrane - chemistry; Cell Membrane - ultrastructure; Cell membranes; cell movement; Cells; Cercopithecus aethiops; COS Cells; crystal structure; Crystallography, X-Ray; Crystals; deformation; Dimers; dynamins; Endocytosis; Liposomes; Membranes; Microscopy, Electron; Molecular Sequence Data; Neurons; P branes; Physiological regulation; Protein Structure, Tertiary; Proteins; src Homology Domains
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1003478107

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, α-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.