Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 294K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2002/9/1153-a $5.00
The Journal of Cell Biology, Volume 158, Number 7, September 30, 2002 1153-a-1153

Finding a heat-shock absorber

Peptide-bound Hsp70 (red) binds cells expressing CD40 (green).

Load the heat-shock protein Hsp70 with a peptide from a tumor-specific antigen, then inject it into a mouse bearing a tumor with the same antigen, and the mouse will mount a vigorous immune response that can significantly reduce tumor progression. The result is promising, but how does it work? Studying human Hsp70, Becker et al. (page 1277) now show that the cell surface protein CD40 binds specifically to peptide-loaded Hsp70, apparently mediating the uptake of the bound peptide into antigen-presenting cells.The binding of Hsp70 to CD40 occurs at the ATPase domain of Hsp70, and is strongly dependent on the presence of a peptide substrate on the heat-shock protein. This could explain why previous efforts, where Hsp70 binding was examined in the absence of nucleotides and peptide substrate, failed to identify the interaction. As the cochaperone protein Hip competes with CD40 for Hsp70 binding, CD40 and Hip apparently recognize overlapping binding sites. The authors propose that the peptide-binding domain of Hsp70, when free of peptide, masks the Hsp70 ATPase domain, thus preventing recognition by CD40. Peptide binding exposes the ATPase domain and allows CD40 to bind, ensuring that only the peptide-bound form of Hsp70 is taken up by antigen-presenting cells for processing.

Alan W. Dove

alanwdove{at}earthlink.net

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes

Thalia Becker, F.-Ulrich Hartl, and Felix Wieland
J. Cell Biol. 2002 158: 1277-1285. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 294K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?