Fig. 4

The Saga of integrins: Integrin binding and activation. Shown is the structure of the unliganded (Inactive) and liganded (Active) αvβ3 integrin with the αv-subunit (chain) in orange and the β3-subunit (chain) in blue. In the inactive form the propeller, I/A, hybrid and thigh domains are bent over towards the carboxyl terminal of the legs of the α- and β-subunits which are inserted through the plasma membrane and connected to short cytoplasmic domains. The organization of the domains are difficult to discern in this configuration but are more easily resolved in the active configuration. In the active form the α- and β-subunits are unfolded freeing the propeller and I/A domains for ligand binding. Activation of the integrin is driven by either ligand binding or by effects on the cytoplasmic domains leading to straightening of the α- and β-subunits and separation of the legs. The straightening of the legs separates the cytoplasmic domains and allows binding of cytoplasmic proteins and intracellular signaling. These changes in integrin configuration are reversible and operate in either direction, outside-in or inside-out