Speaker: Douglas J. Kojetin
Affiliation: Associate Professor Integrative Struct. & Compt’l Biology Scripps Research Inst. Jupiter, FL
Title: Ligand-induced structural dynamics and function of PPARγ learned through NMR
Abstract: Structural studies of nuclear receptor transcription factors have revealed a conserved mechanism for agonist-induced coactivator interaction and transcriptional activation. In contrast, limited structural data indicate that ligand-induced corepressor dependent nuclear receptor repression occurs through structurally diverse mechanisms. Furthermore, the conformational ensemble of the apo/ligand-free nuclear receptor ligand-binding domain, which is hypothesized to exchange between transcriptionally active and repressive conformations, remains poorly characterized. I will discuss our efforts to characterize how small molecule pharmacological ligands—agonists, antagonists, and inverse agonists—influence the conformational ensemble and function of the nuclear receptor PPARγ.