Membrane transport is a fundamental life process that is carried out by membrane channel and transport proteins. We use X-ray crystallography as a primary tool to study the structure and mechanism of medically important membrane transport and channel proteins. The long term goal of our research is to gain a deep understanding of transport mechanism, substrate selectivity and functional regulation. Currently we focus on bacterial proteins that utilize a preexisting proton or sodium gradient to transport their substrates across the cell membrane. We are also interested in integral membrane proteins that transport RNA molecules in eukaryotic cells.
We recently received NIH funding to study Multidrug and Toxin Extrusion (MATE) transporters, which are integral membrane proteins that move structurally unrelated lipophilic cations across the cell membrane by utilizing a preexisting sodium or proton gradient. Bacterial MATE transporters function as multidrug efflux pumps by expelling a cohort of antimicrobial agents from the cytoplasm, whereas their human counterparts mediate the excretion of various cytotoxic metabolites as well as therapeutic drugs. Given their functional relevance to the unwanted resistance to antimicrobials and chemotherapy, molecular structures of the MATE transporters will reveal not only how they transport their substrates across the cell membrane but also how their transport activity can be modulated in order to overcome drug resistance.