Dr. William Dowhan, Professor
and Holder of the John S. Dunn, Sr. Chair

Department of Biochemistry and Molecular Biology
Program in Biochemistry and Molecular Biology

University of Texas-Houston Medical School
P.O. Box 20708 - Houston, Texas 77225
(713) 500-6051: fax (713) 500-0652
email: William.Dowhan@uth.tmc.edu

Ph.D., University of California, Berkeley
American Cancer Society Postdoctoral Fellow, Harvard Medical School

Structure, Function and Assembly of Cell Membranes

A combined molecular genetic and biochemical approach is being used to study the structure, function, and biogenesis of biological membranes in prokaryotic (E. coli) and eukaryotic (yeast) microorganisms. Studies utilizing E. coli focus on understanding biological processes that are similar in both simple and complex organisms. A major goal is to understand the role individual phospholipid species and general membrane phospholipid composition play in cell function. Specific roles for phospholipids at the molecular level have been defined for translocation of proteins across membranes, energy transduction processes, signal transduction, cell division, and the assembly and function of integral membrane proteins. A major emphasis is to understand how membrane proteins interact with their lipid environment to attain final topological organization.

Studies using yeast focus on problems that are unique to eukaryotic systems. Mutants in phospholipid metabolism are being used to study the roles of mitochondrial-specific anionic phospholipids cardiolipin and phosphatidylglycerol in the synthesis, assembly, and function of mitochondrial membrane proteins. A primary role of cardiolipin is to organize components of the electron transport system into supermolecular complexes while both anionic phospholipids are required for the translation of nuclear- and mitochondrial-encoded components of the electron transport chain. View Extended Description of Research Objectives

Webcast of 2005 ASBMB Avanit Award in Lipid Research:
http://www.asbmb.org/ASBMB/site.nsf/Sub/Presentations?opendocument

Xie, J., Bogdanov, M., Heacock, P. and Dowhan, W.: Phosphatidylethanolamine and monoglucosyldiacylglycerol are interchangeable in supporting topogenesis and function of the polytopic membrane protein lactose permease. J. Biol. Chem. 281: 19172-19178 (2006).

Su, X. and Dowhan, W.: Translational Regulation of Nuclear Gene COX4 Expression by Mitochondrial Content of Phosphatidylglycerol and Cardiolipin in Saccharomyces cerevisiae. Mol. Cell. Biol. 26: 743-753 (2006).

Su, X. and Dowhan, W.: Regulation of Cardiolipin Synthase Levels in Saccharomyces cerevisiae. Yeast 23: 279-291 (2006).

Zhang, M, Mileykovskaya, E. and Dowhan, W.: Cardiolipin is essential for organization of complexes III and IV into a supercomplex in intact yeast mitochondria. J. Biol. Chem. 280: 29403-29408, 2005.

Zhang. W., Campbell, H. A., King, S. C. and Dowhan, W.: Phospholipids as determinants of membrane protein topology: Phosphatidylethanolamine is required for the proper topological organization of the g-aminobutyric acid permease (GabP) of Escherichia coli. J. Biol. Chem. 280: 26032-26038, 2005.

Bogdanov, M., Zhang, W., Xie, J., and Dowhan, W.: “Transmembrane protein topology mapping by the substituted cysteine accessibility method (SCAMTM): Application to lipid-specific membrane protein topogenesis.” Methods 36: 148-171, 2005.

Mileykovskaya, E. and Dowhan, W.: Role of membrane lipids in bacterial division site selection. Curr. Opin. Microbiol. 8: 135-142, 2005.

Dowhan, W., Mileykovskaya, E., and Bogdanov, M.: “Diversity and Versatility of Lipid-Protein Interactions Revealed by Molecular Genetic Approaches.” Biochim. Biophys. Acta 1666: 19-39, 2004.

Wikström, M., Xie, J., Bogdanov, M., Mileykovskaya, E., Heacock, P., Wieslander, Å., and Dowhan, W.: Monoglucosyldiacylglycerol, a Foreign Lipid, Can Substitute For Phosphatidylethanolamine in Essential Membrane-Associated Functions in Escherichia coli. J. Biol. Chem. 279: 10284-10292, 2004.

Zhang, W., Bogdanov, M. Pi, J. Pittard, A. J. and Dowhan, W.: Reversible topological organization within a polytopic membrane protein is governed by a change in membrane phospholipid composition. J. Biol. Chem. 278: 50128-50135, 2003.

Mileykovskaya, E., Fishov, I., Fu, X., Corbin, B. D., Margolin, W., and Dowhan, W.: Effects of phospholipid composition on MinD-membrane interactions in vitro and in vivo. J. Biol. Chem. 278:22193-22198, 2003.

Bogdanov, M., Heacock, P. and Dowhan, W.: A polytopic membrane protein displays a reversible topology dependent on membrane lipid composition. EMBO J. 21: 2107-2116, 2002.

Wang, X., Bogdanov, M. and Dowhan, W.: Topology of polytopic membrane protein subdomains is dictated by membrane phospholipid composition. EMBO J. 21: 5673-5681, 2002.

Zhang, M., Mileykovskaya, E., and Dowhan, W.: Gluing the Respiratory Chain Together: Cardiolipin Is Required for Supercomplex Formation in the Inner Mitochondrial Membrane. J. Biol. Chem. 277, 43553-43556, 2002.