Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear Receptors
10.1126/science.280.5370.1747
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

The ligand-binding domain of nuclear receptors contains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactivator proteins. Scanning surface mutagenesis on the human thyroid hormone receptor was performed to define the site that binds the coactivators, glucocorticoid receptor–interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1). The residues involved encircle a small surface that contains a hydrophobic cleft. Ligand activation of transcription involves formation of this surface by folding the carboxyl-terminal α helix against a scaffold of three other helices. These features may represent general ones for nuclear receptors.

Bibliography

Feng, W., Ribeiro, R. C. J., Wagner, R. L., Nguyen, H., Apriletti, J. W., Fletterick, R. J., Baxter, J. D., Kushner, P. J., & West, B. L. (1998). Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear Receptors. Science, 280(5370), 1747–1749.

Authors 9
  1. Weijun Feng (first)
  2. Ralff C. J. Ribeiro (additional)
  3. Richard L. Wagner (additional)
  4. Hoa Nguyen (additional)
  5. James W. Apriletti (additional)
  6. Robert J. Fletterick (additional)
  7. John D. Baxter (additional)
  8. Peter J. Kushner (additional)
  9. Brian L. West (additional)
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  29. We thank M. Stallcup and C. Costa for providing the GST-GRIP1 GST-RXRα and GST-TRβ expression vectors; P. Webb and M. Tsai for providing the pSG5-GRIP1 and pCMX–SRC-1a expression vectors; K. Yamamoto P. Webb M. G. Rosenfeld and T. Scanlan for suggestions; and T. Chen and K. Nakamura for technical assistance. W.F. is a recipient of a postdoctoral fellowship from the National Institutes of Health (DK09516). Supported by NIH grants to J.D.B. (DK51281) and to the Computer Graphics Laboratory at the University of California San Francisco (P41-RR01081).
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:50 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 12:26 a.m.)
Indexed 1 month, 1 week ago (July 26, 2025, 5:30 a.m.)
Issued 27 years, 2 months ago (June 12, 1998)
Published 27 years, 2 months ago (June 12, 1998)
Published Print 27 years, 2 months ago (June 12, 1998)
Funders 0

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@article{Feng_1998, title={Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear Receptors}, volume={280}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.280.5370.1747}, DOI={10.1126/science.280.5370.1747}, number={5370}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Feng, Weijun and Ribeiro, Ralff C. J. and Wagner, Richard L. and Nguyen, Hoa and Apriletti, James W. and Fletterick, Robert J. and Baxter, John D. and Kushner, Peter J. and West, Brian L.}, year={1998}, month=jun, pages={1747–1749} }