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Titolo:
Structure-guided identification of C3d residues essential for its binding to complement receptor 2 (CD21)
Autore:
Clemenza, L; Isenman, DE;
Indirizzi:
Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ochem, Toronto, ON M5S 1A8, Canada
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 7, volume: 165, anno: 2000,
pagine: 3839 - 3848
SICI:
0022-1767(20001001)165:7<3839:SIOCRE>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPSTEIN-BARR VIRUS; T-DEPENDENT ANTIGEN; B-CELL RESPONSE; ANTIBODY-RESPONSE; COMPONENT C3; ACQUIRED-IMMUNITY; ABOLISH BINDING; LYMPHOCYTES-B; 3RD COMPONENT; FACTOR-H;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Isenman, DE Univ Toronto, Dept Biochem, Med Sci Bldg,Room 5306, Toronto, ON M5S 1A8, Canada Univ Toronto Med Sci Bldg,Room 5306 Toronto ON Canada M5S1A8
Citazione:
L. Clemenza e D.E. Isenman, "Structure-guided identification of C3d residues essential for its binding to complement receptor 2 (CD21)", J IMMUNOL, 165(7), 2000, pp. 3839-3848

Abstract

A vital role for complement in adaptive humoral immunity is now beyond dispute, The crucial interaction is that between B cell and follicular dendritic cell-resident complement receptor 2 (CR2, CD21) and its Ag-associated ligands iC3b and C3dg, where the latter have been deposited as a result of classical pathway activation. Despite the obvious importance of this interaction, the location of a CR2 binding site within C3d, a proteolytic limit fragment of C3dg retaining CR2 binding activity, has not been firmly established, The recently determined x-ray structure of human C3d suggested a candidate site that was remote from the site of covalent attachment to Ag and consisted of an acidic residue-lined depression, which accordingly displays a significant electronegative surface potential. These attributes were consistent with the known ionic strength dependence of the CR2-C3d interaction and with the fact that a significant electropositive surface was apparent in a modeled structure of the C3d-binding domains of CR2, Therefore, we have performed an alanine scan of all of the residues within and immediately adjacent to the acidic pocket in C3d, By testing the mutant iC3b molecules for their ability to bind CR2, we have identified two separate clusters of residues on opposite sides of the acidic pocket, specifically E37/E39 and E160/D163/I164/E166, as being important CR2-contacting residues in C3d, Within the second cluster even single mutations cause near total loss of CR2 binding activity. Consistent with the proposed oppositely charged nature of the interface, we have also found that removal of a positive charge immediately adjacent to the acidic pocket (mutant K162A) results in a 2-fold enhancement in CR2 binding activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 14:17:49