Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18).
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.
Ueda
T
T
Department of Medicine, Massachusetts General Hospital, Boston 02129.
Rieu
P
P
Brayer
J
J
Arnaout
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018845:CD11 Antigens / Q000737:chemistry / Q000378:metabolism*; D018821:CD18 Antigens / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D002448:Cell Adhesion; D003179:Complement C3b / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011817:Rabbits; D015183:Restriction Mapping; D013816:Thermodynamics
D018845:CD11 Antigens; D018821:CD18 Antigens; D002413:Cations, Divalent; D016023:Integrins; D046911:Macromolecular Substances; D010455:Peptides; D008345:Manganese; D003179:Complement C3b; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium