Decoding the dual recognition mechanism of the glucocorticoid receptor for DNA and RNA: sequence versus shape.

ABSTRACT: Transcription factors (TFs) regulate eukaryotic transcription through selective DNA-binding, can also specifically interact with RNA, which may present another layer of transcriptional control. The mechanisms of the TFs-DNA recognition are often well-characterised, while the details of TFs-RNA complexation are less understood. Here we investigate the dual recognition mechanism of the glucocorticoid receptor (GR), which interacts with similar affinities with consensus DNA and diverse RNA hairpin motifs but discriminates against uniform dsRNA. Using atomic molecular dynamics simulations, we demonstrate that the GR binding to nucleic acids requires a wide and shallow groove pocket. The protein effectively moulds its binding site within DNA major groove, which enables base-specific interaction

SUBMITTER: Horberg J 

PROVIDER: S-EPMC10522765 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature