%0 Journal Article %J Proc Natl Acad Sci USA %D 2003 %T Structure and allosteric regulation of the αXβ2 integrin I domain %A Vorup-Jensen, T. %A Ostermeier, C. %A Shimaoka, M. %A Hommel, U. %A Springer, T.A. %X

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

%B Proc Natl Acad Sci USA %V 100 %P 1873-1878 %G eng %N 4 %! Proc. Natl. Acad. Sci. U. S. A. %F 451