文章基本信息

标题：Structural implications of Ca2+-dependent actin-bundling function of human EFhd2/Swiprosin-1
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作者：Kyoung Ryoung Park ; Min-Sung Kwon ; Jun Yop An 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep39095
语种：English
出版社：Springer Nature
摘要：EFhd2/Swiprosin-1 is a cytoskeletal Ca(2+)-binding protein implicated in Ca(2+)-dependent cell spreading and migration in epithelial cells. EFhd2 domain architecture includes an N-terminal disordered region, a PxxP motif, two EF-hands, a ligand mimic helix and a C-terminal coiled-coil domain. We reported previously that EFhd2 displays F-actin bundling activity in the presence of Ca(2+) and this activity depends on the coiled-coil domain and direct interaction of the EFhd2 core region. However, the molecular mechanism for the regulation of F-actin binding and bundling by EFhd2 is unknown. Here, the Ca(2+)-bound crystal structure of the EFhd2 core region is presented and structures of mutants defective for Ca(2+)-binding are also described. These structures and biochemical analyses reveal that the F-actin bundling activity of EFhd2 depends on the structural rigidity of F-actin binding sites conferred by binding of the EF-hands to Ca(2+). In the absence of Ca(2+), the EFhd2 core region exhibits local conformational flexibility around the EF-hand domain and C-terminal linker, which retains F-actin binding activity but loses the ability to bundle F-actin. In addition, we establish that dimerisation of EFhd2 via the C-terminal coiled-coil domain, which is necessary for F-actin bundling, occurs through the parallel coiled-coil interaction.