Quansheng Zhu, Ph.D

The AE1 (SLC4A1 gene) anion exchanger is the most abundant protein in red blood cell plasma membrane. I have utilized a cysteine-scanning mutagenesis approach coupled with sulphydryl-specific chemistry to determine the topology of human AE1.  I expressed the mutant AE1 proteins in HEK293 cells and the topology of a given region was determined by comparing cysteine labeling with the membrane-impermeant reagents, qBBr and LYIA. In separate experiments, the transport function of the cysteine AE1 mutants expressed in HEK293 cells was determined. On the basis of these results, a novel topology model was proposed for human AE1 that has been the accepted model up to the present time. I utilized my experience in the experiments  to study the topology of the human electrogenic sodium bicarbonate cotansporter NBCe1. This transporter unlike AE1 does not use an exchange mechanism. The different functional modes of transport and ion substrates suggested that the structure topology would differ also. Indeed this has proven to be true. In a series of experiments, we solved the topology of NBCe1-A,  and showed the potential importance of transmembrane segment 1.m This model has been used to identify where residues that cause pRTA are localized in the protein.

Recent and Selected Publications

Zhu, Q. and Casey, J.R. (2007) Topology of transmembrane proteins by scanning cysteine accessibility mutagenesis methodology. Methods, 41 (4), 439-450. PMID: 17367716.

Zhu, Q., Azimov, R., Kao, L., Newman, D., Liu, W., Abuladze, N., Pushkin, A., Kurtz, I. (2009) NBCe1-A transmembrane segment 1 lines the ion translocation pathway. J. Biol. Chem., 284 (13), 8918-8929. PMID: 19158093. PMCID: PMC2659249.

Tsirulnikov, K., Abuladze, N., Koag, M.C., Newman, D., Scholz, K., Bondar,G., Zhu, Q., Avliyakulov, N.K., Dekant, W., Faull, K., Kurtz, I., and Pushkin, A. (2010) Transport of N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2). Toxicol. Appl. Pharmacol., 244 (2), 218-225. PMID: 20060011. PMCID: PMC2847015.

Zhu, Q., Kao, L., Liu, W., Azimov, R., Pushkin, A., Newman, D., Abuladze, N. and Kurtz, I. (2010) Topological location and structural importance of the NBCe1-A residues mutated in pRTA. J. Biol. Chem., 285 (18), 13416-13426. PMID: 20197274. PMCID: PMC2859501.

Zhu, Q., Azimov, R., Kao, L., Newman, D., Liu, W., Abuladze, N., Pushkin, A., Zhang, C. and Kurtz, I. (2010) Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A. J. Biol. Chem., 285(48), 37178-37187. PMID: 20837482. PMCID: PMC2988324.