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

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

Blog Article

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 VITAMIN E CREAM 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 interactions.Contrary, the GR binding has little effect on the grooves geometry of RNA systems, most notably in uniform dsRNA.

Instead, a hairpin motif in RNA yields a wide and shallow major groove pocket, allowing the protein to anchor itself through nonspecific electrostatic contacts Collections with RNA backbone.Addition of a bulge increases RNA hairpin flexibility, which leads to a greater number of GR-RNA contacts and, thus, higher affinity.Thus, the combination of structural motifs defines the GR-RNA selective binding: a recognition mechanism, which may be shared by other zinc finger TFs.