Published:
Proceedings of the National Academy of Sciences, 2003
Published in:
Proceedings of the National Academy of Sciences, 100 (2003) 4, Seite 1873-1878
Language:
English
DOI:
10.1073/pnas.0237387100
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
The integrin αXβ2 (CD11c/CD18, p150,95) binds ligands through the I domain of the αX subunit. Ligands include the complement factor fragment iC3b, a key component in the innate immune defense, which, together with the expression of αXβ2 on dendritic cells and on other leukocytes, suggests a role in the immune response. We now report the structure of the αX I domain resolved at 1.65 Å by x-ray crystallography. To analyze structural requirements for ligand binding we made a mutation in the αX I domain C-terminal helix, which increased the affinity for iC3b ≈200-fold to 2.4 μM compared with the wild-type domain affinity of ≈400 μM. Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the αX I domain points to the functional importance of this phenomenon.