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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

Team

Principal Investigator

Eric Ortlund
Institution
Emory University

Co-Investigator(s)

Anamika Patel
Institution
Emory University

Team Members

Nancy Meyer
Institution
Oregon Health & Science University

Trevor Moser
Institution
Environmental Molecular Sciences Laboratory