NDLI: Disordered allostery: lessons from glucocorticoid receptor

Content Provider	Springer Nature Link
Author	Motlagh, Hesam N. Anderson, Jeremy A. Li, Jing Hilser, Vincent J.
Copyright Year	2015
Abstract	Allostery is a biological regulation mechanism of significant importance in cell signaling, metabolism, and disease. Although the ensemble basis of allostery has been known for years, only recently has emphasis shifted from interpreting allosteric mechanism in terms of discrete structural pathways to ones that focus on the statistical nature of the signal propagation process, providing a vehicle to unify allostery in structured, dynamic, and disordered systems. In particular, intrinsically disordered (ID) proteins (IDPs), which lack a unique, stable structure, have been directly demonstrated to exhibit allostery in numerous systems, a reality that challenges traditional structure-based models that focus on allosteric pathways. In this chapter, we will discuss the historical context of allostery and focus on studies from human glucocorticoid receptor (GR), a member of the steroid hormone receptor (SHR) family. The numerous translational isoforms of the disordered N-terminal domain of GR consist of coupled thermodynamic domains that contribute to the delicate balance of states in the ensemble and hence in vivo activity. The data are quantitatively interpreted using the ensemble allosteric model (EAM) that considers only the intrinsic and measurable energetics of allosteric systems. It is demonstrated that the EAM provides mechanistic insight into the distribution of states in solution and provides an interpretation for how certain translational isoforms of GR display enhanced and repressed transcriptional activities. The ensemble nature of allostery illuminated from these studies lends credence to the EAM and provides ground rules for allostery in all systems.
Starting Page	257
Ending Page	265
Page Count	9
File Format	PDF
ISSN	18672450
Journal	Biophysical Reviews
Volume Number	7
Issue Number	2
e-ISSN	18672469
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-04-23
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Allostery Intrinsic disorder Glucocorticoid receptor Protein stability Ensemble Biochemistry Biophysics and Biological Physics Cell Biology Membrane Biology Biological Techniques Nanotechnology
Content Type	Text
Resource Type	Article
Subject	Structural Biology Molecular Biology Biophysics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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