Structure and allosteric regulation of the X 2 integrin I domain

The integrin X 2 (CD11c CD18, p150,95) binds ligands through the I domain of the X subunit. Ligands include the complement factor fragment iC3b, a key component in the innate immune defense, which, together with the expression of X 2 on dendritic cells and on other leukocytes, suggests a role in the immune response. We now report the structure of the X I domain resolved at 1.65 Å by x-ray crystallography. To analyze structural requirements for ligand binding we made a mutation in the X I domain C-terminal helix, which increased the affinity for iC3b 200-fold to 2.4 M compared with the wild-type domain affinity of 400 M. Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the X I domain points to the functional importance of this phenomenon.