Open AccessIdentification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18).
Author(s) -
Takashi Ueda,
Philippe Rieu,
Jason Brayer,
M. Amin Arnaout
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.22.10680
Subject(s) - ic3b , integrin alpha m , integrin , ectodomain , complement receptor , homomeric , chemistry , binding site , opsonin , complement system , cd18 , biochemistry , microbiology and biotechnology , biology , protein subunit , receptor , immune system , immunology , in vitro , gene
The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18) with the major complement opsonic C3 fragment iC3b is an important component of the central role of CR3 in inflammation and immune clearance. In this investigation we have identified the iC3b binding site in CR3. A recombinant fragment representing the CR3 A-domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent manner. The iC3b binding site was further localized to a short linear peptide that also bound iC3b directly and inhibited iC3b binding to the A-domain as well as to CR3 expressed by human neutrophils. These data establish a major recognition function for the integrin A-domain and have important implications for development of novel antiinflammatory therapeutics.