Structural basis of the interaction between integrin α6β4 and plectin at the hemidesmosomes

The interaction between the integrin alpha 6 beta 4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane. We describe the crystal structure at 2.75 angstrom A resolution of the primary alpha 6 beta 4-plectin complex, formed by the first pair of fibronectin type III domains and the N-terminal region of the connecting segment of beta 4 and the actin-binding domain of plectin. Two missense mutations in beta 4 (R1225H and R1281W) linked to nonlethal forms of epidermolysis bullosa prevent essential intermolecular contacts. We also present two structures at 1.75 and 2.05 angstrom resolution of the b4 moiety in the absence of plectin, which reveal a major rearrangement of the connecting segment of b4 on binding to plectin. This conformational switch is correlated with the way alpha 6 beta 4 promotes stable adhesion or cell migration and suggests an allosteric control of the integrin.