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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation
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Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation

机译:SH3结构域调节F-BAR介导的膜变形的分子基础

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摘要

Members of the Bin/amphiphysin/Rvs (BAR) domain protein super-family 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-medi-ated regulation of BAR/F-BAR domain function.
机译:Bin / amphiphysin / Rvs(BAR)域蛋白超家族的成员参与从内吞小泡和T管形成到细胞迁移和神经形态发生的各种细胞途径中的膜重塑。膜曲率的诱导和稳定化被编码在BAR或Fer-CIP4同源性BAR(F-BAR)域中,该α-螺旋状卷曲螺旋二聚为膜结合模块。 BAR / F-BAR结构域蛋白通常包含SH3结构域,该结构募集结合伴侣,例如寡聚膜裂变GTPase动力蛋白。尚不清楚如何在细胞水平上调节BAR / F-BAR域介导的膜变形的精确度。在这里,我们介绍了全长syndapin 1及其F-BAR域的晶体结构。我们的数据表明,syndapin 1 F-BAR介导的膜变形受到其SH3结构域的自抑制作用。 syndapin 1 SH3与动力蛋白1富含脯氨酸的结构域之间的缔合驱动着从构象的释放,从而释放了其有效的膜弯曲活性。我们假设该机制可能通常用于调节BAR / F-BAR域诱导的膜变形,并可能将该过程与动力素介导的裂变耦合。因此,我们的数据提出了基于结构的SH3介导的BAR / F-BAR域功能调节模型。

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    Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnDepartment of Neuroscience, Linne Center in Developmental Biology and Regenerative Medicine, Karolinska Institutet, 171.77 Stockholm, Sweden;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnChildren's Medical Research Institute, Wentworthville, New South Wales 2145, Australia;

    rnDepartment of Neuroscience, Linne Center in Developmental Biology and Regenerative Medicine, Karolinska Institutet, 171.77 Stockholm, Sweden;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany;

    rnInstitute of Chemistry and Biochemistry, Freie Universitaet Berlin, 14195 Berlin, Germany Charite Universitatsmedizin Berlin, CC2, 14195 Berlin, Germany Leibniz-Institut fuer Molekulare Pharmakologie, 13125 Berlin, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    dynamin; endocytosis; membrane bending; syndapin;

    机译:动力内吞膜弯曲辛达平;

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