@article {1630950, title = {Regulation by metal ions and the ADMIDAS of integrin α5β1 conformational states and intrinsic affinities}, journal = {Mol Biol Cell}, year = {2022}, month = {2022 Feb 02}, pages = {mbcE21110536}, abstract = {Activation of integrins by Mn2+ is a benchmark in the integrin field, but how it works and whether it reproduces physiologic activation is unknown. We show that Mn2+ and high Mg2+ concentrations compete with Ca2+ at the ADMIDAS and shift the conformational equilibrium toward the open state, but the shift is far from complete. Additionally, replacement of Mg2+ by Mn2+ at the MIDAS increases the intrinsic affinities of both the high affinity open and low affinity closed states of integrins, in agreement with stronger binding of Mn2+ than Mg2+ to oxygen atoms. Mutation of the ADMIDAS increases the affinity of closed states and decreases the affinity of the open state and thus reduces the difference in affinity between the open and closed states. An important biological function of the ADMIDAS may be to stabilize integrins in highly discrete states, so that when integrins support cell adhesion and migration, their high and low affinity correspond to discrete on- and off-states, respectively.}, issn = {1939-4586}, doi = {10.1091/mbc.E21-11-0536}, author = {Anderson, Jordan M and Li, Jing and Springer, Timothy A.} }