Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Multiple discontinuous ligand-mimetic antibody binding sites define a ligand binding pocket in integrin alpha(IIb)beta(3)
Autore:
Puzon-McLaughlin, W; Kamata, T; Takada, Y;
Indirizzi:
Scripps Clin & Res Inst, Dept Vasc Biol, CAL 10, La Jolla, CA 92037 USA Scripps Clin & Res Inst La Jolla CA USA 92037 10, La Jolla, CA 92037 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 11, volume: 275, anno: 2000,
pagine: 7795 - 7802
SICI:
0021-9258(20000317)275:11<7795:MDLABS>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOPROTEIN-IIB-IIIA; MURINE MONOCLONAL-ANTIBODY; DEPENDENT ADHESION SITE; VON-WILLEBRAND-FACTOR; GPIIB-IIIA; PLATELET-AGGREGATION; IIB/IIIA COMPLEX; FIBRINOGEN BINDING; CRITICAL RESIDUES; BETA(3) INTEGRIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Takada, Y Scripps Clin & Res Inst, Dept Vasc Biol, CAL 10, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA Scripps Clin & Res Inst 10666 N Torrey Pines Rd La Jolla CA USA 92037
Citazione:
W. Puzon-McLaughlin et al., "Multiple discontinuous ligand-mimetic antibody binding sites define a ligand binding pocket in integrin alpha(IIb)beta(3)", J BIOL CHEM, 275(11), 2000, pp. 7795-7802

Abstract

Integrin alpha(IIb)beta(3), a platelet fibrinogen receptor, is critically involved in thrombosis and hemostasis. However, how ligands interact with alpha(IIb)beta(3) has been controversial, Ligand-mimetic anti-alpha(IIb)beta(3) antibodies (PAC-1, LJ-CP3, and OP-G2) contain the RGD-like RYD sequencein their CDR3 in the heavy chain and have structural and functional similarities to native ligands. We have located binding sites for ligand-mimetic antibodies in alpha(IIb) and beta(3) using human-to-mouse chimeras, which we expect to maintain functional integrity of alpha(IIb)beta(3). Here we report that these antibodies recognize several discontinuous binding sites;in both the alpha(IIb) and beta(3) subunits; these binding sites are located in residues 156-162 and 229-230 of alpha(IIb) and residues 179-183 of beta(3). In contrast, several nonligand-mimetic antibodies (e.g. 7E3) recognize single epitopes in either subunit, Thus, binding to several discontinuous sites in both subunits is unique to ligand-mimetic antibodies. Interestingly,these binding sites overlap with several (but not all) of the sequences that have been reported to be critical for fibrinogen binding (e.g. N-terminal repeats 2-3 but not repeats 4-7, of alpha(IIb)). These results suggest that ligand-mimetic antibodies and probably native ligands may make direct contact with these discontinuous binding sites in both subunits, which may constitute a ligand-binding pocket.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 10:48:06