The interaction between the integrin alpha6beta4 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 A resolution of the primary alpha6beta4-plectin
complex, formed by the first pair of fibronectin type III domains and the
N-terminal region of the connecting segment of beta4 and the actin-binding
domain of plectin. Two missense mutations in beta4 (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 A resolution of the
beta4 moiety in the absence of plectin, which reveal a major rearrangement of
the connecting segment of beta4 on binding to plectin. This conformational
switch is correlated with the way alpha6beta4 promotes stable adhesion or cell
migration and suggests an allosteric control of the integrin.
