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YONG XIONG

Our laboratory studies innate immune responses to viral infections and mechanisms of fatty acid synthesis. We use a variety of techniques, including X-ray crystallography, biochemistry, molecular biology, and computational biology. We also develop new X-ray crystallographic methods to facilitate the structural work.

Innate immune responses to HIV infection and viral countermeasures
APOBEC3 proteins. The innate immune system is the body's first line of defense against viral infections. Human antiviral protein APOBEC3G induces extensive mutations in HIV DNA that render the virus non-infectious. To evade the host defense system, HIV expresses the virion infectivity factor, Vif, which causes the degradation of APOBEC3G. We aim to establish the chemical and structural principles by which APOBEC3G mutates HIV DNA and the mechanisms by which HIV Vif sequesters APOBEC3G. Information gained from these studies will be used to direct structure-based design of Vif inhibitors that may lead to new anti-HIV drugs.
TRIM5α. Species-specific restriction factors can limit the number of host organisms that retroviruses are able to infect. The tripartite motif protein, TRIM5α, is an important component of the cross-species barrier to HIV and many other retroviruses. TRIM5α likely inhibits retrovirus infection through interactions with the viral capsid protein (CA). The goal of this project is to characterize the TRIM5α-CA interaction in vitro and establish the structural basis for this interaction.

Fatty acid synthesis
De novo synthesis of saturated fatty acids is catalyzed by fatty acid synthase (FAS) through multiple cycles of multi-step reactions. In yeast production of fatty acids is carried out by a 2.6 Megadalton FAS complex that contains 48 reaction centers. We have determined the crystal structure of the yeast FAS in the absence of any substrates. Additional reaction states will be examined to understand the mechanisms of fatty acid synthesis. Information gained can then be used to design FAS inhibitors that may lead to antifungal and obesity therapeutics.

X-ray crystallography at low resolutions
Electron microscope (EM) and X-ray crystallography. X-ray structure determination can utilize a low-resolution EM image for molecular replacement solution followed by phase extension to higher resolution by density modification.
Electron density deblurring. The electron density map obtained by X-ray crystallography or EM is often blurred due to motion and disorder in the crystal. We study the decoupling of the displacement by data sharpening techniques that treat individual domains of the molecule separately.
Folding calculation using X-ray data. Very low-resolution electron density maps (6-8 Å) can be used as a restraint for folding software in de novo calculations of atomic models.

Selected publications:
Xiong, Y., Li, F., Wang, J., Weiner A.M. and Steitz T.A. Crystal structures of an archaeal class I CCA-Adding enzyme and its nucleotide complexes. Mol. Cell 12, 1165-1172 (2003)

Xiong, Y. and Steitz T.A. Mechanism of transfer RNA maturation by CCA-adding enzyme without using an oligonucleotide template. Nature 430, 640-645 (2004)

Li, W., Kamtekar, S., Xiong, Y., Grindley, N.D. and Steitz, T.A. Structure of a synaptic ϒδ resolvase tetramer covalently linked to two cleaved DNAs. Science 309, 1210-1215 (2005)

Xiong, Y. and Steitz T.A. A story with a good ending: tRNA 3’-end maturation by CCA-adding enzymes. Curr Opin Struct Biol. 16, 12-17 (2006)

Lomakin, I. B., Xiong, Y. and Steitz, T. A. The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.  Cell 129, 319-332 (2007)

Last updated 06-27-07