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Updated: May 29, 2026

NMR 15N Relaxation Experiments for the Investigation of Picosecond to Nanoseconds Structural Dynamics of Proteins
Published on: November 1, 2024
Structural dynamics, intrinsic disorder, and allostery in nuclear receptors as transcription factors
Vincent J Hilser1, E Brad Thompson
1Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Abstract:
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.
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