Ligand-induced shifts in conformational ensembles that describe transcriptional activation.

ABSTRACT: Nuclear receptors function as ligand-regulated transcription factors whose ability to regulate diverse physiological processes is closely linked with conformational changes induced upon ligand binding. Understanding how conformational populations of nuclear receptors are shifted by various ligands could illuminate strategies for the design of synthetic modulators to regulate specific transcriptional programs. Here, we investigate ligand-induced conformational changes using a reconstructed, ancestral nuclear receptor. By making substitutions at a key position, we engineer receptor variants with altered ligand specificities. We combine cellular and biophysical experiments to characterize transcriptional activity, as well as elucidate mechanisms underlying altered transcription in receptor va

SUBMITTER: Khan SH 

PROVIDER: S-EPMC9555869 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature