Regulation of integrin α5β1 conformational states and intrinsic affinities by metal ions and the ADMIDAS.

ABSTRACT: Activation of integrins by Mn²⁺ is a benchmark in the integrin field, but how Mn²⁺ works and whether it reproduces physiological 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 dif

SUBMITTER: Anderson JM 

PROVIDER: S-EPMC9265148 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature