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Updated: Mar 2, 2026
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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
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Disordered allostery: lessons from glucocorticoid receptor.
Hesam N Motlagh1, Jeremy A Anderson1, Jing Li1
1T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, 21218, USA.
Biophysical Reviews
|May 17, 2017
Summary
Allostery, a key biological process, is better understood through an ensemble model, especially for intrinsically disordered proteins like human glucocorticoid receptor. This model explains how protein dynamics influence cellular regulation and disease.
Area of Science:
- Biochemistry and Molecular Biology
- Cellular Regulation
- Protein Dynamics
Background:
- Allostery is a crucial biological regulation mechanism.
- Traditional structure-based models struggle with intrinsically disordered proteins (IDPs).
- Recent focus shifts to the statistical nature of allosteric signal propagation.
Purpose of the Study:
- To discuss the historical context of allostery.
- To focus on allosteric regulation in human glucocorticoid receptor (GR).
- To interpret GR isoform activity using the ensemble allosteric model (EAM).
Main Methods:
- Review of historical allostery studies.
- Focus on human glucocorticoid receptor (GR) system.
- Quantitative interpretation using the ensemble allosteric model (EAM).
Main Results:
- IDPs exhibit allostery, challenging traditional models.
- GR's disordered N-terminal domain isoforms show coupled thermodynamic domains.
- EAM quantitatively explains GR isoform activity and state distribution.
Conclusions:
- The ensemble allosteric model (EAM) provides mechanistic insight into allostery.
- EAM unifies allostery in structured, dynamic, and disordered systems.
- EAM offers ground rules for understanding allostery across biological systems.
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