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WIENER LABORATORY home > about > wiener
 
 
UofVirginia

University of Virginia
Molecular Physiology & Biological Physics Dept.
Jordan Hall, PO Box 800736
Charlottesville, VA 22908
434-924-5108


 

virginia_groupDr. Michael C. Wiener is an Associate Professor in the Department of Molecular Physiology & Biological Physics in the University of Virginia’s School of Medicine.

The goal of Dr. Wiener’s research is to solve x-ray crystal structures of channel, transport and receptor proteins, and to use these structures in conjunction with other results to understand the molecular basis of function of these integral membrane proteins.  Structural studies of TMP targets in the Wiener laboratory include:

1. Aquaporins (AqpZ)
Protein-mediated water transport is a fundamental physiological process in all organisms that is carried out by aquaporins.  Aquaporins serve as passive, diffusion-limited channels to dissipate osmotic gradients that form across cell membranes.  The Wiener laboratory has obtained crystals of human aquaporin hAQP1 that diffract to 4Å resolution, and high-level expression of the E. coli homolog AqpZ has also been attained.  The Wiener laboratory has published a detailed characterization of AqpZ expression, solubilization, and purification [1].  AqpZ is stable in many detergents, and more than fifty different crystallization conditions have been identified.

2. The outer membrane transporter BtuB
Gram-negative bacteria possess specialized transport pathways for the binding and uptake of essential organometallic cofactors.  An outer membrane transporter couples to an inner membrane “motor”.  One of the motor proteins, TonB, couples to the outer membrane transporter, and utilizes the inner membrane proton-motive force in a mechanical force transduction mechanism to drive substrate through the outer membrane transporter.  The Wiener laboratory has solved several structures of the E. coli cobalamin outer membrane transporter BtuB [2] and has done extensive analysis of the structures of BtuB and other TonB-dependent transporters [3, 4].  The structure of a BtuB:TonB 1:1 complex has also been solved [5].

References

1. Mohanty, A.K. and M.C. Wiener, Membrane protein expression and production: effects of polyhistidine tag length and position. Protein Expr Purif, 2004. 33(2): p. 311-25. (PMID:14711520)
2. Chimento, D.P., A.K. Mohanty, R.J. Kadner, and M.C. Wiener, Substrate-induced transmembrane signaling in the cobalamin transporter BtuB. Nat Struct Biol, 2003. 10(5): p. 394-401. (PMID: 12652322)
3. Chimento, D.P., R.J. Kadner, and M.C. Wiener, The Escherichia coli outer membrane cobalamin transporter BtuB: structural analysis of calcium and substrate binding, and identification of orthologous transporters by sequence/structure conservation. J Mol Biol, 2003. 332(5): p. 999-1014. (PMID: 14499604)
4. Chimento, D.P., R.J. Kadner, and M.C. Wiener, Comparative structural analysis of TonB-dependent outer membrane transporters: implications for the transport cycle. Proteins, 2005. 59(2): p. 240-51. (PMID: 15739205)
5. Shultis, D.D., M.D. Purdy, C.N. Banchs, and M.C. Wiener, Outer membrane active transport: structure of the BtuB:TonB complex. Science, 2006. 312(5778): p. 1396-9. (PMID: 16741124)