Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin β4
Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin β4
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DOI：
10.1016/s0969-2126(03)00090-x
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发表时间：
2003-06-01
期刊：
影响因子：
5.7
通讯作者：
de Pereda, JM
中科院分区：
文献类型：
--
作者：
García-Alvarez, B;Bobkov, A;de Pereda, JM
Plectin是一种广泛表达的细胞骨架连接物。在这里，我们报道了plectin的肌动蛋白结合区域的晶体结构，并表明该区域足以与F-actin或整合素α 6β 4的细胞质区域相互作用。该结构由两个钙钙蛋白同源结构域排列成一个封闭的构象。我们发现，与f -肌动蛋白的结合诱导了plectin的构象变化，这种变化被工程结构域间二硫桥抑制。提出了两步诱导配合机制，包括结合和随后的结构域重排。相反，与整合素alpha6beta4的相互作用以封闭的构象发生。粘附素与f -肌动蛋白和整合素α 6β 4的竞争性结合可能依赖于观察到的可选结合机制，涉及变构和位阻因素。
Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors.