5i2q
Structure of EF-hand containing proteinStructure of EF-hand containing protein
Structural highlights
FunctionEFHD2_HUMAN May regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis. Plays a role as negative regulator of the canonical NF-kappa-B-activating branch. Controls spontaneous apoptosis through the regulation of BCL2L1 abundance. Publication Abstract from PubMedEFhd2/Swiprosin-1 is a cytoskeletal Ca2+-binding protein implicated in Ca2+-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 Ca2+ 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 Ca2+-bound crystal structure of the EFhd2 core region is presented and structures of mutants defective for Ca2+-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 Ca2+. In the absence of Ca2+, 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. Structural implications of Ca2+-dependent actin-bundling function of human EFhd2/Swiprosin-1.,Park KR, Kwon MS, An JY, Lee JG, Youn HS, Lee Y, Kang JY, Kim TG, Lim JJ, Park JS, Lee SH, Song WK, Cheong HK, Jun CD, Eom SH Sci Rep. 2016 Dec 15;6:39095. doi: 10.1038/srep39095. PMID:27974828[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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