Journal article
Radicicol-sensitive peptide binding to the N-terminal portion of GRP94
The Journal of biological chemistry, v 277(43), pp 40742-40750
25 Oct 2002
PMID: 12189140
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
GRP94 is a molecular chaperone that carries immunologically relevant peptides from cell to cell, transferring them to major histocompatibility proteins for presentation to T cells. Here we examine the binding of several peptides to recombinant GRP94 and study the regulation and site of peptide binding. We show that GRP94 contains a peptide-binding site in its N-terminal 355 amino acids. A number of peptides bind to this site with low on- and off-rates and with specificity that is distinct from that of another endoplasmic reticulum chaperone, BiP/GRP78. Binding to the N-terminal fragment is sufficient to account for the peptide binding activity of the entire molecule. Peptide binding is inhibited by radicicol, a known inhibitor of the chaperone activities of HSP90-family proteins. However, the peptide-binding site is distinct from the radicicol-binding pocket, because both can bind to the N-terminal fragment simultaneously. Furthermore, peptide binding does not cause the same conformational change as does binding of radicicol. When the latter binds to the N-terminal domain, it induces a conformational change in the downstream, acidic domain of GRP94, as measured by altered gel mobility and loss of an antibody epitope. These results relate the peptide-binding activity of GRP94 to its other function as a chaperone.
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Details
- Title
- Radicicol-sensitive peptide binding to the N-terminal portion of GRP94
- Creators
- Shawn Vogen - University of ChicagoTali Gidalevitz - From the Department of Pathology and the Committees on Cell Physiology andChhanda Biswas - From the Department of Pathology and the Committees on Cell Physiology andBirgitte B Simen - From the Department of Pathology and the Committees on Cell Physiology andEytan Stein - From the Department of Pathology and the Committees on Cell Physiology andFunda Gulmen - University of ChicagoYair Argon - University of Chicago
- Publication Details
- The Journal of biological chemistry, v 277(43), pp 40742-40750
- Publisher
- ASBMB Publications / Elsevier
- Grant note
- HL 07237 / NHLBI NIH HHS DK 07074 / NIDDK NIH HHS CA 74182 / NCI NIH HHS GM 07183 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000178791400076
- Scopus ID
- 2-s2.0-0037174940
- Other Identifier
- 991020100087404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology