Single Point Mutation in Bin/Amphiphysin/Rvs (BAR) Sequence of Endophilin Impairs Dimerization, Membrane Shaping, and Src Homology 3 Domain-mediated Partnership
| Autor: | Anne A. Schmidt, Mabel Jouve San-Roman, Anna Gortat, Christian Vannier |
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| Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientique (CNRS),Centre National de la Recherche Scientique (CNRS),ACI BCMS 2004 2 421 from the French Ministry of Research, Association pour la Recherche sur le Cancer (ARC), La Ligue National contre le Cancer, Comité de Paris |
| Rok vydání: | 2012 |
| Předmět: |
genetic structures
Membrane lipids Endocytic recycling [SDV.BC]Life Sciences [q-bio]/Cellular Biology Protomer Biology Biochemistry Protein Structure Secondary SH3 domain Quantitative Biology::Subcellular Processes src Homology Domains Cell membrane Mice 03 medical and health sciences 0302 clinical medicine Physics::Atomic and Molecular Clusters medicine Animals Humans Point Mutation BAR domain [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Protein Structure Quaternary Molecular Biology endophilins 030304 developmental biology 0303 health sciences High Energy Physics::Phenomenology Cell Membrane Cell Biology medicine.anatomical_structure Amino Acid Substitution Membrane curvature membrane curvature Amphiphysin Biophysics Condensed Matter::Strongly Correlated Electrons Mathematics::Differential Geometry Protein Multimerization Acyltransferases 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, epub ahead of print. ⟨10.1074/jbc.M111.325837⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | International audience; Bin/Amphiphysin/Rvs (BAR) domain-containing proteins are essential players in the dynamics of intracellular compartments. The BAR domain is an evolutionarily conserved dimeric module characterized by a crescent-shaped structure whose intrinsic curvature, flexibility and ability to assemble into highly ordered oligomers, contribute to inducing curvature of target membranes. Endophilins, diverging into A and B sub-groups, are BAR and SH3 domain-containing proteins. They exert activities in membrane dynamic processes such as endocytosis, autophagy, mitochondrial dynamics and permeabilization during apoptosis. Here, we report on the involvement of the third α-helix of endophilins A BAR sequence in dimerization and identify leucine 215 as a key residue within a network of hydrophobic interactions stabilizing the entire BAR dimer interface. With the combination of amino-terminal truncation retaining the high dimerization capacity of the third α-helices of endophilins A and leucine 215 substitution by aspartate (L215D), we demonstrate the essential role of BAR-sequence mediated dimerization on SH3 domain partnership. In comparison to wild type, full-length endophilin A2 heterodimers with one protomer bearing the L215D substitution, exhibit very significant changes in membrane-binding and shaping activities as well as dramatic decrease of SH3 domain partnership. This suggests that subtle changes in the conformation and/or rigidity of the BAR domain impact on both the control of membrane curvature and downstream binding to effectors. Finally, we show that expression, in mammalian cells, of endophilin A2 bearing the L215D substitution, impairs the endocytic recycling of transferrin receptors. |
| Databáze: | OpenAIRE |
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