Nuclear Receptor Research


Ligand-Induced Allosteric Effects Governing SR Signaling

Author(s): C. Denise Okafor, Jennifer K. Colucci, and Eric A. Ortlund

Steroid receptors (SRs) are a class of ligand-regulated transcription factors that regulate gene expression in response to the binding of steroid hormones. Ligand binding drives conformational changes within the SR ligand binding domain that alters the receptors' affinity for coregulator proteins that in turn modulate chromatin state and either promote or block the recruitment of transcriptional machinery to a gene. Structural characterizations of SRs have provided insight into how these conformational rearrangements modulate receptor function, including signaling between the ligand binding pocket and the site of coregulator binding. Here, we review some of the proposed structural mechanisms put forward to explain the ability of ligands to modulate SR function. We also provide a discussion on computational methods that have contributed to the elucidation of SR allosteric regulation. Finally, we consider broader discussions of allostery within the SR family, such as receptor-induced reverse allostery and allosteric binding sites located outside of the canonical ligand interaction site.