Structure and allosteric regulation of the αXβ2 integrin I domain

The integrin alphaXbeta2 (CD11c/CD18, p150,95) binds ligands through the I domain of the alphaX subunit. Ligands include the complement factor fragment iC3b, a key component in the innate immune defense, which, together with the expression of alphaXbeta2 on dendritic cells and on other leukocytes, suggests a role in the immune response. We now report the structure of the alphaX I domain resolved at 1.65 Angstrom by x-ray crystallography. To analyze structural requirements for ligand binding we made a mutation in the alphaX I domain C-terminal helix, which increased the affinity for iC3b approximate to200-fold to 2.4 muM compared with the wild-type domain affinity of approximate to400 muM. Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the alphaX I domain points to the functional importance of this phenomenon.