Title: Spectroscopic Definition of the Requirements for Heme Binding and Dimerization of PGRMC1

By: Katlyn Meier, PhD

Assistant Professor, Department of Chemistry at the University of Miami, FL

Abstract:

Metals are ubiquitous in nature. In fact, more than 30% of all proteins require a metal for proper folding or function. In this talk, I will focus on how my lab uses a range of spectroscopic characterization tools to define the role of metals in protein structure and formation of dynamic protein-protein complexes. Specifically, I will present our recent work related to the progesterone receptor membrane component 1 (PGRMC1) protein, which binds heme and is thought to interact with downstream cytochrome P450s to disrupt drug metabolism and cholesterol synthesis. Recent work has called into question the heme-triggered formation of the PGRMC1 dimer that is thought to be critical for these interactions. Using a combination of spectroscopic techniques (circular dichroism, fluorescence, electron paramagnetic resonance, size exclusion chromatography), we characterized the heme-PGRMC1 interaction at the secondary, quaternary, and metal-centric levels. We also prepared several variants (C129S

and Y113F) to precisely define the contributions of disulfide bonding and heme-heme stacking to PGRMC1 dimerization. The results of these studies shed light on how the PGRMC1 monomer and dimer may participate in downstream protein−protein interactions, and provide critical insight needed to develop design principles for potential therapeutics that target PGRMC1 dimerization.

Lunch will be provided.