Molecular basis for SH3 domain regulation of F-BAR–mediated membrane deformation
Open accessAbstract
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.
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Syndapin is a peripheral membrane protein located in the SSR and its F-bar domain may contribute to the folding and tubulation of this postsynaptic membrane network.
“Syndapin is a peripheral membrane protein located in the SSR and its F-bar domain may contribute to the folding and tubulation of this postsynaptic membrane network (Kumar et al, 2009;Wang et al, 2009;Rao et al, 2010).”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Rao et al, 2010
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Meinecke, M., Boucrot, E., Camdere, G., Hon, W.-C., Mittal, R., & McMahon, H. T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444869 · Cited by 155 · see citing works
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Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst
Teodoro, R. O., Pekkurnaz, G., Nasser, A., Higashi‐Kovtun, M. E., Balakireva, M., McLachlan, I. G., Camonis, J., & Schwarz, T. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.147 · Cited by 61 · see citing works
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- Authors
- Rao, Y., Ma, Q., Vahedi-Faridi, A., Sundborger, A., Pechstein, A., Puchkov, D., Luo, L., Shupliakov, O., Saenger, W., & Haucke, V.
- Affiliations
- Freie Universität Berlin (DE)
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany;
- Karolinska Institutet (SE)
- Children's Medical Research Institute (AU)
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-19
- Volume
- 107
- Issue
- 18
- Pages
- 8213-8218
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889545
- OpenAlex
- W1972849666
- Cited by
- 149
- References
- 1
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 2 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 9 · 2013: 15 · 2012: 14
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- HZB Repository (Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB)) (submittedVersion)
- Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion)
- Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- F-BAR domain, SH3 domain, dynamin 1, membrane deformation, membrane curvature, BAR domain proteins, autoinhibition, proline-rich region, crystal structure, membrane fission, protein-protein interaction regulation
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Membrane, Chlorocebus aethiops, Microscopy, Electron, Molecular Sequence Data, Protein Structure, Tertiary, Crystallography, X-Ray, src Homology Domains, COS Cells
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