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

ABSTRACT: 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 Mg²⁺ 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 Mg²⁺-binding site establish long-range couplings, leading to both pH- and Mg²⁺-occupancy-dependent biphasic stability change in the αX I-domain fold. The ligand-binding sensorgrams show composite affinity events for the αX I-domain accounting for the multiplicity of the αX I-domain conformational states existing in the solution.

SUBMITTER: Manandhar P 

PROVIDER: S-EPMC9440770 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature