Tuesday, November 18 | 11:00 a.m. – Noon
Classroom Building 170

Studying the molecular mechanisms of a human ABC transporter during physiologically relevant conditions

ATP-Binding Cassette (ABC) transporters play important physiological roles by using energy from ATP to translocate a large diversity of substrates across biological membranes. Despite years of research, the detailed molecular mechanisms coupling ATP hydrolysis with substrate binding and translocation remain poorly understood. Most of the currently available structural models are obtained under experimental conditions that favor certain conformations, which may not be prevalent during physiological functioning. In my group, we aim at improving our mechanistic understanding by interrogating these transporters using a spectroscopy ruler (Luminescence Resonance Energy Transfer or LRET) that allows to measure distance between probes strategically placed in regions of interest along the protein. Our approach consists of directly correlating the ATP hydrolysis of the purified transporter reconstituted in a phospholipids bilayer (nanodiscs), with the conformational changes of the protein determined under identical physiologically relevant experimental conditions. I will be presenting our data describing the conformational equilibrium of a human mitochondrial ABC transporter (ABCB10), which is essential for heme biosynthesis and for protection against oxidative stress. Also, we use mutagenesis of critical residues in the substrate binding pocket as a useful tool to understand substrate specificity and to dissect interactions that may lead to conformational changes associated with ATP hydrolysis and/or substrate binding. Our goal is obtaining a general overview of the protein’s molecular mechanism of transport under physiologically relevant conditions.

About the Speaker

Maria Elena Zoghbi is a biologist from the Central University of Venezuela, with a PhD in Physiology and Biophysics from the Venezuelan Institute for Scientific Research. For her doctoral research and first postdoctoral position, she studied the structure of myosin thick filaments by electron microscopy at the University of Massachusetts Medical School. Then, ATP-Binding cassette (ABC) transporters became the focus of her research during her second postdoctoral position at Texas Tech University Health Sciences Center in Lubbock. Maria is currently an Associate Professor in the Department of Molecular and Cell Biology at UC Merced, where her research program focuses on the molecular study of ABC transporters by biochemical and biophysical approaches under physiologically relevant conditions.