Structural and Functional Analysis of the Actin Binding Domain of Plectin Suggests Alternative Mechanisms for Binding to F-Actin and Integrin β4
2003; Elsevier BV; Volume: 11; Issue: 6 Linguagem: Inglês
10.1016/s0969-2126(03)00090-x
ISSN1878-4186
AutoresBegoña García‐Álvarez, Andrey A. Bobkov, Arnoud Sonnenberg, José M. de Pereda,
Tópico(s)Silk-based biomaterials and applications
ResumoPlectin 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.
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