@article {746696, title = {Relating conformation to function in integrin α5β1}, journal = {Proc Natl Acad Sci U S A.}, year = {2016}, month = {17 Jun 2016}, abstract = { Whether β1\ integrin ectodomains visit conformational states similarly to β2\ and β3\ integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to β1\ integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin α5β1\ ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the α5\ or β1\ legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the β1\ βI domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open βI domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the βI domain and βI-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of α5β1\ is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to α5β1\ on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.}, url = {http://www.pnas.org.ezp-prod1.hul.harvard.edu/content/early/2016/06/16/1605074113.long}, author = {Su, Yang and Xia, Wei and Li. Jing and Walz, Thomas and Humphries, Martin J. and Vestweber, Dietmar and Caba{\~n}as, Carlos and Lu, Chafen and Springer, T.A.} }