ABCG5 and ABCG8 are recently identified members of a superfamily of ATP-driven transporters that actively translocate a wide variety of substances (from anions and other small molecules to entire proteins) across membranes. ABCG5 and ABCG8 are presumably form a heterodimer for its function within cells, and are implicated to play important roles in sterol transport. The focus of this project in the lab is the biochemistry and molecular characterization of ABCG5 and ABCG8, aiming at several fundamental issues such as the functional form and enzymatic property of this pair of ABC transporters, identification of the direct transport substrate and other components of this transport system.
Another recently established research project in the lab is the regulatory pathway of surface-exposure of phosphatidylserine (PS) during apoptosis and the molecular mechanism of aminophospholipid translocation. The phospholipid composition in plasma membrane of most eukaryotic cells is asymmetric. Aminophospholipids including PS are primarily present in the inner leaflet of plasma membrane, and the exposure of PS to the outer leaflet serves as a cellular signal during apoptosis and blood coagulation, but the proteins involved in this process remain to be determined. Our aim in this project is to identify the enzymes responsible for this regulated aminophospholipid transport.
Our traditional project is the clathrin-coated vesicle proton translocating ATPase, a member of the V-type proton pump family present in all eukaryotic cells. Within cells, members of V-type proton pumps are localized to a wide variety of intracellular organelles and plasma membranes for some specialized cells, and are responsible for the establishment and maintenance of pH differentiation between different subcellular compartments. This enzyme is a large multi-subunit membrane protein. The main goal of our research team in this project is to understand the structure, function, and regulation of V-type proton pumps, with approaches at different levels of biochemistry, cell biology, and molecular biology.
RESEARCH INTERESTS
Structure and function of V-type Proton translocating ATPase.
Biochemistry of ABC transporters-ABCG5 and ABCG8.
RECENT PUBLICATIONS
Xiaochen Wang, Jin Wang, Keiko Gengyo-Ando, Lichan Gu, Chen-Ling sun, Chonglin Yang, Yong Shi, TetsuoKobayashi, Yigong Shi, Shohei Mitani, Xiao-Song Xie, and Ding Xue, "C. elegans mitochondrial factor WAH-1 promotes PS externalization in apoptotic cells through phospholipid scramblase SCRM-1" Nature Cell Biology, Vol. 9:pp.541-549, May 2007
Jin Wang, Fang Sun, Da-wei Zhang, Yongming Ma, Fang Xu, Jitendra belani, Jonathan Cohen, Helen, Hobbs, and Xiao-Song Xie, "Sterol Transfer by ABCG5 and ABCG8" Journal of Biologicla Chemistry, Vol. 281:pp.27894-27904, September 2006
Marco Gregorini, Jin Wang, Xiao-Song Xie, Ronald, Milligan, Andreas, Engel, "Three-dimensional reconstruction of bovine brain V-ATPase by cryo-electron microscopy and single particle analysis" Journal of Structural Biology, Vol. 158:pp.445-454, June 2007
Xie, X.-S., Padron, D., Liao, X., Wang, J., Roth, M.G., De Brabander, J.K., "Salicylihalamide A inhibits the Vo sector of the V-ATPase through a mechanism distinct from Bafilomycin A1" Journal of Biological Chemistry, 279:19755-19763, May 2004
Crider, B. and Xie, X.-S., "Characterization of the functional coupling of bovine brain V-ATPase: Effect of divalent cations, phospholipids, and subunit H(SFD)" Journal of Biological Chemistry, 278:44281-44288, November 2003
SIGNIFICANT PUBLICATIONS
Xiaochen Wang, Jin Wang, Keiko Gengyo-Ando, Lichan Gu, Chen-Ling sun, Chonglin Yang, Yong Shi, TetsuoKobayashi, Yigong Shi, Shohei Mitani, Xiao-Song Xie, and Ding Xue, "C. elegans mitochondrial factor WAH-1 promotes PS externalization in apoptotic cells through phospholipid scramblase SCRM-1" Nature Cell Biology, Vol. 9:pp.541-549, May 2007
Jin Wang, Fang Sun, Da-wei Zhang, Yongming Ma, Fang Xu, Jitendra belani, Jonathan Cohen, Helen, Hobbs, and Xiao-Song Xie, "Sterol Transfer by ABCG5 and ABCG8" Journal of Biologicla Chemistry, Vol. 281:pp.27894-27904, September 2006
Marco Gregorini, Jin Wang, Xiao-Song Xie, Ronald, Milligan, Andreas, Engel, "Three-dimensional reconstruction of bovine brain V-ATPase by cryo-electron microscopy and single particle analysis" Journal of Structural Biology, Vol. 158:pp.27894-27904, June 2007
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