Faculty

Zhaohui Xu

Associate Professor of Biological Chemistry and Research Associate Professor of Life Sciences

Ph.D., University of Minnesota
Postdoctoral Fellow, Yale University

Research Focus: Molecular Complexes; Membrane Trafficking; Breast Cancer

Phone: 734.615.2077
E-mail: zhaohui@umich.edu
Fax: 734.936.6492

The goal of our laboratory is to understand the structure and function of molecular complexes in the cell.  Proteins function in the cell through interaction with other molecules.  Understanding the structure, energetics and regulation of protein complex formation in specific cellular processes will provide fundamental insights into the molecular mechanisms underlying these cellular processes and provide means for therapeutic intervention of related diseases.

Our current focus is on the Endosomal Sorting Complexes Required for Trafficking (ESCRTs).  The ESCRT proteins are important in number of mechanistically related cellular processes including MVB biogenesis, HIV virus budding, cytokinesis and autophagy.  The ESCRT proteins forms molecular complexes on the biological membrane to induce membrane curvature generation and vesicle budding.  These complexes are released from the membrane via the activity of AAA-ATPase Vps4 which provides the only energy input in the entire process, thereby serves as an important point of regulation.  Vps4 is regulated in the cell through the binding of regulatory proteins including Vta1, Vps60, Did2 and Ist1.  We are using a combination of biochemical, biophysical, cell biology and genetic approaches to understand the molecular mechanism of Vps4 regulation.

Xu Research Group

 

Awards

2001
Pew Scholar in Biomedical Sciences

 

Representative Publications

  1. Guo, E. Z. and Xu, Z. (2015) Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains. J. Biol. Chem290, 8396-8408. PMCID: PMC4375492

  2. Vild, C. J., Li, Y., Guo, E. Z., Liu, Y., and Xu, Z. (2015) A Novel Mechanism of Regulating the ATPase VPS4 by Its Cofactor LIP5 and the Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein CHMP5. J. Biol. Chem290, 7291-7303. PMCID: PMC4358147

  3. Davies, B. A., Norgan, A. P., Payne, J. A., Schulz, M. E., Nichols, M. D., Tan, J. A., Xu, Z., and Katzmann, D. J. (2014) Vps4 stimulatory element of the cofactor Vta1 contacts the ATPase Vps4 alpha7 and alpha9 to stimulate ATP hydrolysis. J. Biol. Chem. 289, 28707-28718. PMCID: PMC4192519

  4. Vild, C. J. and Xu, Z. (2014) Vfa1 binds to the N-terminal Microtubule Interacting and Trafficking (MIT) domain of Vps4 and stimulates its ATPase activity. J. Bio. Chem 289, 10378-10386. PMCID: PMC4036160

  5. Norgan, A. P., Davies, B. A., Azmi, I. F., Schroeder, A. S., Payne, J. A., Lynch, G. M., Xu, Z., Katzmann, D. J. (2013) Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4 stimulatory element. J. Bio. Chem 288, 26147-26156. PMCID: PMC3764817

 

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