Detail: | Abstract:
Resistance-nodulation-cell division efflux pumps are integral membrane proteins that catalyze the export of substrates across cell membranes. Within the hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division proteins largely form trimeric efflux pumps. The drug efflux process has been proposed to entail a synchronized motion between subunits of the trimer to advance the transport cycle, leading to the extrusion of drug molecules. Here we use X-ray crystallography and single-molecule fluorescence resonance energy transfer imaging to elucidate the structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump. We find that the CmeB trimer displays a very unique conformation. A direct observation of transport dynamics in individual CmeB trimers embedded in membrane vesicles indicates that each CmeB subunit undergoes conformational transitions uncoordinated and independent of each other. On the basis of our findings and analyses, we propose a model for transport mechanism where CmeB protomers function independently within the trimer.
Biosketch:
Dr. Edward Yu received his Ph.D. from the University of Michigan at Ann Arbor in 1997 and followed by an NIH postdoctoral fellowship at the University of California-Berkeley. Dr. Yu joined the faculty at Iowa State University in 2004 and is currently a professor of Chemistry and of Physics & Astronomy. He was named the John D. Corbett Professor of Chemistry in 2014 and was elected as a Fellow of the American Association for the Advancement of Science that same year. Dr. Yu's research program focuses on elucidating the phenomenon of antimicrobial resistance in bacteria and the structure-function of membrane proteins using x-ray crystallography. |
