Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB
Document Type
Article
Publication Title
Nature Communications
Abstract
The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB.
DOI
10.1038/s41467-022-34892-4
Publication Date
12-1-2022
Recommended Citation
Murray, Meghan H.; Valfort, Aurore Cecile; Koelblen, Thomas; Ronin, Céline; Ciesielski, Fabrice; Chatterjee, Arindam; Veerakanellore, Giri Babu; Elgendy, Bahaa; Walker, John K.; Hegazy, Lamees; and Burris, Thomas P., "Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB" (2022). Pharmaceutical and Administrative Sciences Faculty Publications. 81.
https://doi.org/10.1038/s41467-022-34892-4
https://collections.uhsp.edu/pharm-admin-sciences_pubs/81
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