Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster

JianFeng Chen, Azucena Salas, Timothy A Springer
2003 Nature Structural & Molecular Biology  
Integrin ␣ 4 ␤ 7 mediates rolling adhesion in Ca 2+ and Ca 2+ + Mg 2+ , and firm adhesion in Mg 2+ and Mn 2+ , mimicking the two key steps in leukocyte accumulation in inflamed vasculature. We mutated an interlinked linear array of three divalent cation-binding sites present in integrin ␤-subunit I-like domains. The middle, metal ion-dependent adhesion site (MIDAS) is required for both rolling and firm adhesion. One polar site, that adjacent to MIDAS (ADMIDAS), is required for rolling because
more » ... r rolling because its mutation results in firm adhesion. The other polar site, the ligand-induced metal binding site (LIMBS), is required for firm adhesion because its mutation results in rolling. The LIMBS mediates the positive regulatory effects of low Ca 2+ concentrations, whereas the ADMIDAS mediates the negative regulatory effects of higher Ca 2+ concentrations, which are competed by Mn 2+ . The bipolar sites thus stabilize two alternative phases of adhesion.
doi:10.1038/nsb1011 pmid:14608374 fatcat:okzh4a4rsffuzmseyhp4ip6xzq