biostudies-literatureVorup-Jensen TNCI NIH HHS1873-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC149926biostudies-literatureUnknown100(4)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.Proceedings of the National Academy of Sciences of the United States of AmericaStructure and allosteric regulation of the alpha X beta 2 integrin I domain.PMC149926R01 CA031799CA31799Springer TAVorup-Jensen TOstermeier CShimaoka MHommel UfalseStructure and allosteric regulation of the alpha X beta 2 integrin I domain.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.2003-01-01T00:00:00Z2003 Feb2024-12-03T21:52:50.952Z2019-10-26T17:17:45ZS-EPMC1499261255482910.1073/pnas.0237387100