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Titolo:
Binding of antigenic peptide to the endoplasmic reticulum-resident proteingp96/GRP94 heat shock chaperone occurs in higher order complexes - Essential role of some aromatic amino acid residues in the peptide-binding site
Autore:
Linderoth, NA; Simon, MN; Hainfeld, JF; Sastry, S;
Indirizzi:
Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA Rockefeller Univ New York NY USA 10021 Genet Lab, New York, NY 10021 USA Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA Brookhaven Natl Lab Upton NY USA 11973 ab, Dept Biol, Upton, NY 11973 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 14, volume: 276, anno: 2001,
pagine: 11049 - 11054
SICI:
0021-9258(20010406)276:14<11049:BOAPTT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CRYSTAL-STRUCTURES; SH2 DOMAIN; GP96 GRP94; HSP90; RECEPTOR; FAMILY; FORMS; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Sastry, S Rockefeller Univ, Mol Genet Lab, 1230 York Ave, New York, NY 10021 USA Rockefeller Univ 1230 York Ave New York NY USA 10021 Y 10021 USA
Citazione:
N.A. Linderoth et al., "Binding of antigenic peptide to the endoplasmic reticulum-resident proteingp96/GRP94 heat shock chaperone occurs in higher order complexes - Essential role of some aromatic amino acid residues in the peptide-binding site", J BIOL CHEM, 276(14), 2001, pp. 11049-11054

Abstract

Vaccination with heat shock protein gp96-antigenic peptide complexes produces a powerful specific immune response against cancers and infectious diseases in some experimental animal models, and gp96-peptide complexes are nowbeing tested in human clinical trials. gp96 appears to serve as a natural adjuvant for chaperoning antigenic peptides into the immune surveillance pathways. A fundamental issue that needs to be addressed is the mechanism of binding of antigenic peptide to gp96, Here, we show using scanning transmission electron microscopy that recombinant gp96 binds peptide in stable multimeric complexes, which may have biological significance. To open the possibility for genetically engineering gp96 for improved immunogenicity and to understand if molecular recognition plays a role in the binding of antigenic peptide, we mutagenized some specific aromatic amino acids in the presumed peptide-binding pocket. Replacement of Tyr-667 or Tyr-678 to Ala reduced affinity for peptide whereas conversion of Trp-654 to Tyr increased peptidebinding. Similarly, changing Trp-621 to Phe or Leu or Ala or lie negatively affected peptide binding whereas changing Trp-621 to Tyr or Val positively affected peptide binding, Probing the peptide microenvironment in gp86-peptide complexes, suggested that hydrophobic interactions land perhaps hydrogen bonding/stacking interactions) may play a role in peptide loading by gp96.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 04:03:05