title: Distinct recognition of complement iC3b by integrins αXβ2and αMβ2.
abstract: Recognition by the leukocyte integrins αXβ2and αMβ2of complement iC3b-opsonized targets is essential for effector functions including phagocytosis. The integrin-binding sites on iC3b remain incompletely characterized. Here, we describe negative-stain electron microscopy and biochemical studies of αXβ2and αMβ2in complex with iC3b. Despite high homology, the two integrins bind iC3b at multiple distinct sites. αXβ2uses the αXαI domain to bind iC3b on its C3c moiety at one of two sites: a major site at the interface between macroglobulin (MG) 3 and MG4 domains, and a less frequently used site near the C345C domain. In contrast, αMβ2uses its αI domain to bind iC3b at the thioester domain and simultaneously interacts through a region near the αMβ-propeller and β2βI domain with a region of the C3c moiety near the C345C domain. Remarkably, there is no overlap between the primary binding site of αXβ2and the binding site of αMβ2on iC3b. Distinctive binding sites on iC3b by integrins αXβ2and αMβ2may be biologically beneficial for leukocytes to more efficiently capture opsonized pathogens and to avoid subversion by pathogen factors.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215.
authors.forename: Shutong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
authors.forename: Jianchuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215; springer_lab@crystal.harvard.edu jwang@crystal.harvard.edu.|Department of Pediatrics, and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215.
authors.forename: Jia-Huai
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; springer_lab@crystal.harvard.edu jwang@crystal.harvard.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D001665:Binding Sites; D003179:Complement C3b / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D017434:Protein Structure, Tertiary
chemical_list: D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D003179:Complement C3b