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Allosteric Regulation and Intrinsic Disorder in Nuclear Hormone Receptors

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Nuclear Receptors: From Structure to the Clinic

Abstract

Nuclear Hormone Receptors (NHRs) must respond to a variety of chemical cues to selectively induce or repress pertinent genes. Each domain of these multidomain proteins is capable of binding to various large or small molecules, and such binding may alter the activity of both the local and remote domains. These allosteric effects are essential for proper NHR function; yet until recently very little was known about their mechanism. Recent well-documented findings show that protein dynamics and intrinsic disorder mediate allosteric signals. We discuss the recently proposed Ensemble Allosteric Model, which can be used to mechanistically dissect perplexing and sometimes paradoxical allosteric phenomena. Finally, we show how this model can be specifically applied to NHRs and how its use can enhance future studies.

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Acknowledgments

VJH is supported by NIH grant GM063747 and NSF grant MCB-0446050. JTW was supported by the NIH training grant 5T32GM007231-39 to the Johns Hopkins University department of biology. HNM was supported by the NIH training grant T32-GM008403.

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Authors and Affiliations

  1. Department of Biology, Johns Hopkins University, 21218, Baltimore, MD, USA

    Jordan T. White & Vincent J. Hilser

  2. T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA

    Hesam N. Motlagh, Jing Li & Vincent J. Hilser

  3. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 77204-5056, Houston, TX, USA

    E. Brad Thompson

  4. Prof. Emeritus, University of Texas Medical Branch, Galveston, TX, USA

    E. Brad Thompson

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  1. Jordan T. White
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  5. Vincent J. Hilser
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Correspondence to Vincent J. Hilser .

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  1. School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Iain J. McEwan

  2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania, USA

    Raj Kumar

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White, J., Motlagh, H., Li, J., Thompson, E., Hilser, V. (2015). Allosteric Regulation and Intrinsic Disorder in Nuclear Hormone Receptors. In: McEwan, I., Kumar, R. (eds) Nuclear Receptors: From Structure to the Clinic. Springer, Cham. https://doi.org/10.1007/978-3-319-18729-7_5

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