The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.

ABSTRACT: Nuclear receptors (NRs) are transcription factors that regulate essential biological processes in response to cognate ligands. An important part of NR function involves ligand-induced conformational changes that recruit coregulator proteins to the activation function surface (AFS), ~15 Å away from the ligand-binding pocket. Ligands must communicate with the AFS to recruit appropriate coregulators and elicit different transcriptional outcomes, but this communication is poorly understood. These studies illuminate allosteric communication networks underlying activation of liver receptor homolog-1 (LRH-1), a NR that regulates development, metabolism, cancer progression, and intestinal inflammation. Using >100 μs of all-atom molecular dynamics simulations involving 74 LRH-1 complexes, we identi

SUBMITTER: Mays SG 

PROVIDER: S-EPMC10510465 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature