The Arg non-receptor tyrosine kinase modifies F-actin structure
The Arg non-receptor tyrosine kinase modifies F-actin structure
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DOI：
10.1016/j.jmb.2004.11.078
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发表时间：
2005-02-18
影响因子：
5.6
通讯作者：
Egelman, EH
中科院分区：
文献类型：
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作者：
Galkin, VE;Orlova, A;Egelman, EH
Arg（精氨酸相关基因）蛋白属于调节细胞运动和形态发生的非受体酪氨酸激酶Abl家族。它包含两个肌动蛋白结合结构域，一个包含talin样I/LWEQ基序，和一个C-末端钙调蛋白同源（CH）结构域。我们使用电子显微镜和单粒子图像分析，以重建复合物的F-肌动蛋白与全长精氨酸，片段缺乏I/LWEQ或CH域。Arg CH结构域与肌动蛋白的亚结构域1（SDI）结合并诱导肌动蛋白原聚体的倾斜。I/LWEQ结构域与SDI或SD4结合，关闭肌动蛋白的核苷酸结合裂缝。虽然Arg可以使用其CH或ILWEQ结构域结合肌动蛋白丝，但Arg内的两个结构域不能同时结合到丝中的相邻原聚体，这与其F-肌动蛋白成束活性一致。精氨酸引起的微丝构象变化可以解释精氨酸与F-肌动蛋白的协同结合，并可能阻止其他肌动蛋白结合蛋白与肌动蛋白微丝的结合。(C)2004爱思唯尔有限公司保留所有权利。
The Arg (Abl-related gene) protein belongs to the Abl family of nonreceptor tyrosine kinases that regulate cell motility and morphogenesis. It contains two actin-binding domains, one containing the talin-like I/LWEQ motif, and a C-terminal calponin homology (CH) domain. We used electron microscopy and single particle image analysis to reconstruct complexes of F-actin with full-length Arg, and fragments lacking either the I/LWEQ or CH domains. The Arg CH domain binds to actin's subdomain-1 (SDI) and induces a tilt of actin protomers. The I/LWEQ domain binds to either SDI or SD4, closing the nucleotide binding cleft of actin. Although Arg can use either its CH or ILWEQ domains to bind an actin filament, both domains within Arg cannot bind simultaneously to adjacent protomers in the filament, consistent with its F-actin-bundling activity. The conformational changes in the filament introduced by Arg can explain the cooperative binding of Arg to F-actin and might prevent other actin binding proteins from binding to actin filaments. (C) 2004 Elsevier Ltd. All rights reserved.