Imaging Transcriptional Complexes by CryoEM
EMSL Project ID
51309
Abstract
Nuclear receptors (NRs) sense changes in lipid metabolite levels to trigger specific patterns of gene regulation, which drive critical biological processes including metabolism, development, and inflammation. Liver receptor homolog-1 (LRH-1) is a NR that senses phospholipid (PL) species to control a host of metabolic genes; this makes it an attractive target for the treatment of metabolic disorders. LRH-1-mediated gene regulation relies upon multiple factors, including its abilities to sense PLs, bind DNA, and partner with transcriptional coregulatory proteins. Significant progress has been made in structurally characterizing LRH-1’s ligand- and DNA-binding mechanisms using isolated domains, however, no high-resolution information exists describing how full-length LRH-1, or any NRs, interact with coregulators to form the functional transcriptional supercomplexes that regulate gene expression. These large transcriptional complexes are difficult?to assemble and?often too?dynamic?for?X-ray crystallography, however, structural data is achievable with Cryo-EM. The objective here is to capture atomic-level structural information of LRH-1 transcriptional supercomplexes to visualize the conformational changes that dictate transcriptional output.
Project Details
Start Date
2020-03-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members