The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments.
J Biol Chem
; 276(46): 42667-76, 2001 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-11544255
ABSTRACT
Human and simian immunodeficiency viruses infect host lymphoid cells by binding CD4 molecules via their gp160 envelope glycoproteins. Biochemical studies on recombinant SIVmac32H (pJ5) envelope ectodomain gp140 precursor protein show that the envelope is a trimer. Using size exclusion chromatography, quantitative amino acid analysis, analytical ultracentrifugation, and CD4-based competition assay, we demonstrate that the stoichiometry of CD4 receptor-oligomeric envelope interaction is 11. By contrast, Fab fragments of both neutralizing and non-neutralizing monoclonal antibodies bind at a 31 ratio. Thus, despite displaying equivalent CD4 binding sites on each of the three gp140 protomers within an uncleaved trimer, only one site binds the soluble 4-domain human CD4 extracellular segment. The anti-cooperativity and the faster k(off) of gp140 trimerCD4 versus gp120 monomerCD4 interaction suggest that CD4-induced conformational change is impeded in the intact envelope. The implications of these findings for immunity against human immunodeficiency virus and simian immunodeficiency virus are discussed.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Fragmentos Fab das Imunoglobulinas
/
Glicoproteínas
/
Antígenos CD4
/
Produtos do Gene env
/
Proteínas Oncogênicas de Retroviridae
/
Proteínas Virais de Fusão
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos