Heterotropic roles of divalent cations in the establishment of allostery and affinity maturation of integrin αXβ2.

Allosteric activation and silencing of leukocyte β2-integrins transpire through cation-dependent structural changes, which mediate integrin biosynthesis and recycling, and are essential to designing leukocyte-specific drugs. Stepwise addition of Mg reveals two mutually coupled events for the αXβ2 ligand-binding domain-the αX I-domain-corresponding to allostery establishment and affinity maturation. Electrostatic alterations in the Mg-binding site establish long-range couplings, leading to both pH- and Mg-occupancy-dependent biphasic stability change in the αX I-domain fold.