title: Structure and allosteric regulation of the alpha X beta 2 integrin I domain.
abstract: 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.
authors.affiliation: Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorup-Jensen
authors.forename: Christian
authors.initials: C
authors.lastname: Ostermeier
authors.forename: Motomu
authors.initials: M
authors.lastname: Shimaoka
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hommel
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001483:Base Sequence; D018360:Crystallography, X-Ray; D017931:DNA Primers; D016167:Integrin alphaXbeta2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D017931:DNA Primers; D016167:Integrin alphaXbeta2; D011994:Recombinant Proteins