Allosteric Regulation and Intrinsic Disorder in Nuclear Hormone Receptors

White, Jordan T.; Motlagh, Hesam N.; Li, Jing; Thompson, E. Brad; Hilser, Vincent J.

doi:10.1007/978-3-319-18729-7_5

Nuclear Receptors: From Structure to the Clinic 2015

DOI: 10.1007/978-3-319-18729-7_5

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Allosteric Regulation and Intrinsic Disorder in Nuclear Hormone Receptors

Jordan T. White

Hesam N. Motlagh

Jing Li

et al.

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2018

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Cited by 2 publications

References 124 publications

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Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor

White

Grasso

et al. 2018

Phil. Trans. R. Soc. B

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Allostery is an important regulatory phenomenon enabling precise control of biological function. Initial understanding of allostery was gained from seminal work on conformational changes exhibited by structured proteins. Within the last decade, protein allostery has also been demonstrated to occur within intrinsically disordered proteins. This emerging concept of disorder-mediated allostery can be usefully understood in the context of a thermodynamic ensemble. The advantage of this ensemble allosteric model is that it unifies the explanations of allostery occurring within both structured and disordered proteins. One central finding from this model is that energetic coupling, the transmission of a signal between separate regions (or domains) of a protein, is maximized when one or more domains are disordered. This is due to a disorder-order transition that contributes additional coupling energy to the allosteric system through formation of a molecular interaction surface or interface. A second key finding is that multiple interfaces may constructively or destructively interfere with each other, resulting in a new form of allosteric regulation called 'energetic frustration'. Articulating protein allostery in terms of the thermodynamic ensemble permits formulation of experimentally testable hypotheses which can increase fundamental understanding and direct drug-design efforts. These ideas are illustrated here with the specific case of human glucocorticoid receptor, a medically important multi-domain allosteric protein that contains both structured and disordered regions and exemplifies 'energetic frustration'.This article is part of a discussion meeting issue 'Allostery and molecular machines'.

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Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor

White

Grasso

et al. 2018

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

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Estrogen Receptors: New Directions in the New Millennium

2018

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Nineteen years have passed since our previous review in this journal in 1999 regarding estrogen receptors. At that time, we described the current assessments of the physiological activities of estrogen and estrogen receptors. Since that time there has been an explosion of progress in our understanding of details of estrogen receptor-mediated processes from the molecular and cellular level to the whole organism. In this review we discuss the basic understanding of estrogen signaling and then elaborate on the progress and current understanding of estrogen receptor actions that have developed using new models and continuing clinical studies.

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Allosteric Regulation and Intrinsic Disorder in Nuclear Hormone Receptors

Cited by 2 publications

References 124 publications

Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor

Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor

Estrogen Receptors: New Directions in the New Millennium

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