Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Unliganded and Hormone-Bound Glucocorticoid Receptors Interact with Distinct Hydrophobic Sites in the Hsp90 C-Terminal Domain

L. Fang, D. Ricketson, L. Getubig and B. Darimont
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 49 (Dec. 5, 2006), pp. 18487-18492
Stable URL: http://www.jstor.org/stable/30051140
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Unliganded and Hormone-Bound Glucocorticoid Receptors Interact with Distinct Hydrophobic Sites in the Hsp90 C-Terminal Domain
Preview not available

Abstract

Unlike most chaperones, heat-shock protein 90 (Hsp90) interacts with a select group of "client proteins" that regulate essential biological processes. Little is known about how Hsp90 recognizes and binds these proteins. The glucocorticoid receptor (GR) is a well characterized Hsp90 client protein, whose hormone binding, nuclear-cytoplasmic trafficking, and transcriptional activity are regulated by Hsp90. Here, we provide evidence that unliganded and hormone-bound GR interact with two distinct, solventexposed hydrophobic sites in the Hsp90 C-terminal domain that contain the sequences "MxxIM" (HM10) and "L/MxxIL" (HMg9). Our results indicate that binding of Hsp90 HM10 to unliganded GR stabilizes the unliganded ligand-binding pocket of GR indirectly by promoting an intramolecular interaction between the C-terminal α-helix (H12) and a solvent-exposed hydrophobic groove in the GR ligand binding domain. In the presence of hormone, Hsp90 appears to bind the hydrophobic groove of GR directly by mimicking the interactions of GR with transcriptional coactivators. The identified interactions provide insights into the mechanisms that enable Hsp90 to regulate the activity of both unliganded and hormonebound GR and to sharpen the cellular response to hormone.

Page Thumbnails

  • Thumbnail: Page 
18487
    18487
  • Thumbnail: Page 
18488
    18488
  • Thumbnail: Page 
18489
    18489
  • Thumbnail: Page 
18490
    18490
  • Thumbnail: Page 
18491
    18491
  • Thumbnail: Page 
18492
    18492