Nuclear receptor interdomain communication is mediated by the hinge with ligand specificity.

ABSTRACT: Nuclear receptors are ligand-induced transcription factors that bind directly to target genes and regulate their expression. Ligand binding initiates conformational changes that propagate to other domains, allosterically regulating their activity. The nature of this interdomain communication in nuclear receptors is poorly understood, largely owing to the difficulty of experimentally characterizing full-length structures. We have applied computational modeling approaches to describe and study the structure of the full length farnesoid X receptor (FXR), approximated by the DNA binding domain (DBD) and ligand binding domain (LBD) connected by the flexible hinge region. Using extended molecular dynamics simulations (> 10 microseconds) and enhanced sampling simulations, we provide evidence that

SUBMITTER: Hazarika S 

PROVIDER: S-EPMC10888817 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature