Lan Guan

Texas Tech Univeristy Health Sciences Center, USA

Title: Cooperative binding mechanism is the core of co-transport catalyzed by melibiose transporter MelB

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Biography

Lan Guan, MD, PhD, Professor and Interim Chair, Department of Cell Physiology and Molecular Biophysics, and Director, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Her research has been funded by federal grants with a focus on molecular mechanisms of ion-coupled nutrient transporters using X-ray crystallography, single-particle cryo-EM, ligand binding thermodynamics, genetic engineering, and many other biochemical & biophysical analyses. Her laboratory determined the first 3-D high-resolution crystal structure of a Na+-coupled major facilitator superfamily transporter. She published 91 peer-reviewed research articles, reviews, and book chapters.

Abstract

Secondary active transporters contain a large group of symporters that utilize the free energy installed in an electrochemical ion gradient across the cell membranes to catalyze uptake of varied solutes. Co-transport of solutes with cations is obligatory, but the principles underlying the cotransport is not well understood. We used a model system, the bacterial melibiose symporter MelB that couples melibiose uptake with the entry of H⁺, Na⁺, or Li⁺, to study Na⁺-coupled symport mechanisms. By determining high-resolution crystal structures of MelB and analyzing ligand binding, thermodynamics, and transport kinetics, it could be concluded that cooperative binding mechanism is the core of co-transport. It regulates the function of the transporter and ensures the obligatory symport. The positive cooperativity between the driving cation and driven substrate allows the transporters to catalyze uptakes effectively in substrate-limited environments.