Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4.
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.
García-Alvarez
Begoña
B
Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bobkov
Andrey
A
Sonnenberg
Arnoud
A
de Pereda
José M
JM
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051190:Plectin; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013816:Thermodynamics
D000199:Actins; D039663:Integrin beta4; D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin