Structural Dynamics, Intrinsic Disorder, and Allostery in Nuclear Receptors as Transcription Factors

Steroid hormone receptors (SHRs) and nuclear receptors (NRs) in general are flexible, allosterically regulated transcription factors. The classic model is inadequate to explain all their behavior. Keys to function are their regions of intrinsic disorder (ID). Data show the dynamic structure and allo...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2011-11, Vol.286 (46), p.39675-39682
Main Authors: Hilser, Vincent J., Thompson, E. Brad
Format: Article
Language:English
Subjects:
Allosteric Regulation
Allosteric Regulation - physiology
Animals
Glucocorticoid Receptor
Humans
Intrinsically Disordered Proteins
Ligands
Minireviews
Nuclear Receptors
Protein Ensembles
Protein Structure, Tertiary
Receptors, Steroid - chemistry
Receptors, Steroid - metabolism
Response Elements - physiology
SERM
Steroid Hormone Receptor
Structure-Activity Relationship
TMAO
Transcription Factors
Transcription Factors - chemistry
Transcription Factors - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Steroid hormone receptors (SHRs) and nuclear receptors (NRs) in general are flexible, allosterically regulated transcription factors. The classic model is inadequate to explain all their behavior. Keys to function are their regions of intrinsic disorder (ID). Data show the dynamic structure and allosteric interactions of the three classic SHR domains: ligand-binding (LBD), DNA-binding (DBD), and N-terminal (NTD). Each responds to its ligands by stabilizing its structure. The LBD responds to classic steroidal and nonsteroidal small ligands; both may selectively modify SHR activity. The DBD responds differentially to the DNA sequences of its response elements. The NTD, with its high ID content and AF1, interacts allosterically with the LBD and DBD. Each domain binds heterologous proteins, potential allosteric ligands. An ensemble framework improves the classic model, shows how ID regions poise the SHR/NR family for optimal allosteric response, and provides a basis for quantitative evaluation of SHR/NR actions.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.R111.278929