本周四23日，在中区医学楼210会议室，金腾川教授邀请了来自美国Case Western Researve University 药学院的Edward Yu 教授作了题为“Structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump”的报告。
图：Edward Yu教授（左）和金腾川教授（右）合影留念
Edward Yu教授主要利用结构生物学手段，研究病原微生物特别是多重耐药细菌的耐药泵的结构和功能关系。
报告摘要：
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.
代表性论文
1.Yu, E. W., G. McDermott, H. I. Zgurskaya, H. Nikaido, and D. E. Koshland, Jr. 2003. Structural Basis of Multiple Drug-Binding Capacity of the AcrB Multidrug Efflux Pump. Science 300:976- 980.
2.*C.-C. Su, *F. Long, M. T. Zimmermann, K. R. Rajashankar, R. L. Jernigan, and E. W. Yu. 2011. Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558-562. (Reviewed by F1000).
3. *Su, C.-C., *J. R. Bolla, *N. Kumar, *A. Radhakrishnan, *F. Long, *J. A. Delmar, *T.-H. Chou, K. R. Rajashankar, W. M. Shafer and E. W. Yu. 2015. Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps. Cell Reports. 11:61-70. (Made the cover of the issue)
4. *Bolla, J. R., *C.-C. Su, *J. A. Delmar, *A. Radhakrishnan, *N. Kumar, *T.-H. Chou, *F. Long, K. R. Rajashankar and E. W. Yu. 2015. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology. Nature Commun. 6:6874. (doi:10.1038/ncomms7874)
5. *Su, C.-C., L. Yin, *N. Kumar, L. Dai, *A. Radhakrishnan, *T.-H. Chou, K. R. Rajashankar, Q. Zhang, Y.-K. Shin and E. W. Yu. 2017. Structures and transport dynamics of a multidrug efflux pump in Campylobacter jejuni. Nature Commun. 8:171. doi:10.1038/s41467-017-00217-z.
金腾川课题组
2017.11.24
