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

Yijian Rao, Qingjun Ma, Ardeschir Vahedi-Faridi, Anna Sundborger, Arndt Pechstein, Dmytro Puchkov, Lin Luo, Oleg Shupliakov, Wolfram Saenger, Volker Haucke

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


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 conformationis 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.

Original languageEnglish (US)
Pages (from-to)8213-8218
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - May 4 2010
Externally publishedYes


  • Dynamin
  • Endocytosis
  • Membrane bending
  • Syndapin


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