Edward Yu, PhD

Professor
Department of Pharmacology
School of Medicine

Since I began my tenure track position in 2004, I have developed a highly successful independent research program that focuses on the structure, assembly and mechanism of the resistance-nodulation-cell division (RND)-superfamily efflux pumps as well as their regulation. These efflux pumps are key components for Gram-negative pathogens to ensure their survival in toxic environments by extruding a variety of antimicrobial agents from bacterial cells. Typically, RND efflux pumps work in conjunction with a periplasmic membrane fusion protein and an outer membrane channel to form a functional protein complex. One such RND-type efflux system is the Escherichia coli CusCFBA tetrapartite heavy-metal efflux system, which specifically recognizes and confers resistance to Ag(I) and Cu(I) ions. My lab has determined the crystal structures of the CusA heavy-metal efflux pump. We have also resolved the crystal structure of the CusBA adaptor-transporter efflux complex. This is the only adaptor-transporter efflux complex structure that has been determined using X-ray crystallography. In addition, we have determined two mutant structures of the CusC efflux channel, reviewing conformational changes accompanying folding and transmembrane channel formation of this outer membrane protein. Because of the efflux pump works that I accomplished, I was invited to edit a book entitled “Microbial Efflux Pumps: Current Research“ (Caister Academic Press, 2013). I was also invited to write an annual review on bacterial multidrug efflux transporters. Recently, I focus on elucidating the structure and function of the Burkholderia multivorans HpnN hopanoid transporter, which is a member of a subfamily of the RND-superfamily transporters. The HpnN membrane protein plays a predominant role in supporting membrane stability and barrier function, thus contributing to multidrug resistance. Having solved the structure of HpnN, I reasoned that we could develop compounds that block its function. Indeed, we have made considerable progress in this arena and we are now in an excellent position to pursue the identification and function of novel peptides that are able to inhibit the function of this transporter.

Publications

1.    Long, F., C.-C. Su, M.T. Zimmermann, S.E. Boyken, K.R. Rajashankar, R.L. Jernigan, and E.W. Yu. 2010. Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport. Nature 467:484-488. PMCID: PMC2946090

2.    Su, C.-C., 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. PMCID: PMC3078058

3.    Bolla, J., S.V. Do, F. Long, L. Dai, C.-C. Su, H.-T. Lei, X. Chen, J.E. Gerkey, D.C. Murphy, K.R. Rajashankar, Q. Zhang, and E. W. Yu. 2012. Structural and functional analysis of the transcriptional regulator Rv3066 of Mycobacterium tuberculosis. Nucl. Acids Res. 40:9340-9355. PMCID: PMC3467072

4.    Delmar, J.A., C.-C. Su and E.W. Yu. 2014. Bacterial multi-drug efflux transporters. Annu. Rev. Biophys. 43:93-117. PMCID: PMC4769028

5.    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 Rep. 11:61-70. PMCID: PMC4410016

6.    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. PMCID: PMC4410182

7.    Kumar, N., C.-C. Su, C.-C., T.-H. Chou, A. Radhakrishnan, J.A. Delmar, K.R. Rajashankar and E.W. Yu. 2017. Crystal structures of the Burkholderia multivorans hopanoid transporter HpnN. Proc. Natl. Acad. Sci. USA 114:6557-6562. PMCID: PMC5488925

8.    Su, C.-C., L. Yin, N. Kumar, L. Dai, A. Radhakrishnan, J. R. Bolla, H.-T. Lei, T.-H. Chou, J.A. Delmar, 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. PMCID: PMC5537355