Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains.

ABSTRACT: Integrins are transmembrane cell-extracellular matrix adhesion receptors that impact many cellular functions. A subgroup of integrins contain an inserted (I) domain within the α-subunits (αI) that mediate ligand recognition where function is contingent on binding a divalent cation at the metal ion dependent adhesion site (MIDAS). Ca²⁺ is reported to promote α1I but inhibit α2I ligand binding. We co-crystallized individual I-domains with MIDAS-bound Ca²⁺ and report structures at 1.4 and 2.15 Å resolution, respectively. Both structures are in the "closed" ligand binding conformation where Ca²⁺ induces minimal global structural changes. Comparisons with Mg²⁺-bound structures reveal Mg²⁺ and Ca²⁺ bind α1I in a manner sufficient

SUBMITTER: Brown KL 

PROVIDER: S-EPMC5811549 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature