5 April 2024
Denise Okafor
Department of Biochemistry and Molecular Biology
Pennsylvania State University
The farnesoid X receptor is a ligand-regulated transcription factor that controls genes important for bile acid, lipid, and glucose metabolism. Like other nuclear receptors, allostery is a critical aspect of FXR function. Ligands of diverse shapes and sizes selectively modulate the transcriptional output of FXR by influencing the distantly located DNA binding domain. Our laboratory aims to understand how ligand binding (LBD) and DNA binding domains (DBD) of FXR 'talk to one another' to permit ligand-specific transcriptional outcomes. We combine molecular dynamics simulations with biochemical experiments to elcuidate interdomain communication and allostery. Our findings have allowed us to generate, to our knowledge, the first models for how ligand identity is communicated from LBD to DBD. I will discuss the state of knowledge regarding interdomain allostery in nuclear receptors in general, our recent findings, and our ongoing work towards this goal.