Atypical interactions of integrin α V β 8 with pro-TGF-β1

Significance Integrins are cell-surface molecules that link extracellular ligands to the cytoskeleton. Force exerted by the cytoskeleton that is resisted by the ligand is thought to be important in activating the integrin by stabilizing an extended-open conformational state with high affinity for ligand. However, integrin α V β 8 does not interact with the cytoskeleton in the same way. Here, we show that, although the closely related integrins α V β 8 and α V β 6 bind the same ligand, pro-TGF-β1, their conformational responses to ligand binding and regulation by metal ions are quite different. These differences correlate with their distinct linkage to the cytoskeleton.