Relating conformation to function in integrin α 5 β 1

Significance β 1 integrins form the largest and most diverse integrin subfamily, with 12 distinct αβ heterodimers. Together, the seven other integrin β-subunits form an equal number of 12 heterodimers. Despite speculation that different integrin subfamilies may differ in activation mechanism or conformation, we show that α 5 β 1 , similar to β 2 and β 3 integrins, can adopt the bent-closed, extended-closed, and extended-open overall global conformational states. We characterize nine function-perturbing antibodies for the subunit and domain they bind and the conformation they stabilize. Only the extended-open α 5 β 1 conformation mediates adhesion to fibronectin. Our results enable many cell biological studies on the 12 β 1 integrins to be interpreted in terms of the integrin conformational states on cell surfaces that are stabilized.