Faculty Profile
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Christopher Fraser
ASSISTANT PROFESSOR Molecular and Cellular Biology (College of Biological Sciences) Office 530-752-1716 Lab 530-752-1714 csfraser@ucdavis.edu |
Degrees:
1999 - PhD - University of Sussex - Biochemistry
1995 - BS - University of Sussex - Biology
Awards:
Wellcome Trust Prize Studentship 1995-1998
Department and Center Affiliations:
Molecular and Cellular Biology
Grad Group Affiliations and Specialties:
Biochemistry and Molecular Biology
Publications:
Fraser, C. S., Hershey, J. W., and Doudna, J. A. The pathway of hepatitis C virus mRNA recruitment to the human ribosome. Nat. Struct. Mol. Biol. 2009 Apr;16(4):397-404.
Zhou, M., Sandercock, A. M., Fraser, C. S., Ridlova, G., Stephens, E, Schenauer, M. R., Yokoi-Fong, T., Barsky, D., Leary, J. A., Hershey, J. W., Doudna, J. A., and Robinson, C. V. Mass Spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3. Proc. Natl. Acad. Sci. U S A. 2008 Nov 25;105(47):18139-44.
Poyry, T. A. A., Kaminski, A., Connell, E., Fraser, C. S., and Jackson, R. J. The mechanism of an exceptional case of reinitiation after translation of a long open-reading frame reveals why such events do not generally occur in mammalian mRNA translation. Genes Dev. 2007 Dec 1;21(23):3149-62.
Fraser, C. S., Berry, K. E., Hershey, J. W., and Doudna, J. A. eIF3j is located in the decoding center of the human 40S ribosomal subunit. Mol. Cell. 2007 Jun 22;26(6):811-9.
Fraser, C. S., and Doudna, J. A. Quantitative studies of ribosome conformational dynamics. Q. Rev. Biophys. 2007 May;40(2):163-89.
Damoc, E., Fraser, C. S., Zhou, M., Videler, H., Mayeur, G. L., Hershey, J. W., Doudna, J. A., Robinson, C. V., and Leary, J. A. Structural Characterization of the Human Eukaryotic Initiation Factor 3 Protein Complex by Mass Spectrometry. Mol. Cell Proteomics. 2007 Jul;6(7):1135-1146.
Fraser, C. S., and Doudna, J. A. Structural and mechanistic insights into Hepatitis C viral translation initiation. Nat. Rev. Microbiol. 2007 Jan;5(1):29-38.
Siridechadilok, B., Fraser, C. S., Hall, R. J., Doudna, J. A., and Nogales, E. Structural Roles for Human Translation Factor eIF3 in Initiation of Protein Synthesis. Science. 2005 Dec 2;310(5753):1513-5.
Fraser, C. S., and Hershey, J. W. B. Movement in Ribosome Translocation. J. Biol. 2005, 4:8
Ji, H., Fraser, C. S., Yu, Y., Leary, J., and Doudna, J. A. Coordinated assembly of human translation initiation complexes by the Hepatitis C Virus internal ribosome entry site RNA. Proc. Natl. Acad. Sci. U. S. A. 2004 Dec 7;101(49):16990-5.
Fraser, C. S., Lee, J. Y., Mayeur, G. L., Bushell, M., Doudna, J. A., and Hershey, J. W. B. The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40S ribosomal subunits in vitro. J. Biol. Chem. 2004 Mar 5;279(10):8946-56.
Mayeur, G. L., Fraser, C. S., Pieretti, F., Block, K. L., and Hershey, J. W. B. Characterization of eIF3k, a newly discovered subunit of mammalian translation initiation factor eIF3. Eur. J. Biochem. 2003 Oct 15; 270(20): 4133-4139.
Daughenbaugh, K. F., Fraser, C. S., Hershey, J. W. B., and Hardy, M. E. The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment. EMBO J. 2003 Jun 2;22(11):2852-9.
Fraser, C. S., Pain, V. M., and Morley, S. J. Cellular stress in Xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein. Biochem. J. 1999 Sep 15; 342 Pt 3:519-26.
Fraser, C. S., Pain, V. M., and Morley, S. J. The association of initiation factor 4F with poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells. J. Biol. Chem. 1999 Jan 1; 274(1):196-204.
Research Interests:
The regulation of protein synthesis plays a major role in controlling gene expression and consequently cell growth, proliferation and differentiation. Rates of protein synthesis are altered in response to nutrient availability, hormones and growth factors and therefore are directly coupled with cell cycle progression. Proteins catalyze most of the reactions on which life depends, so it is of no surprise that there are many links between the dysregulation of protein synthesis and disease progression. Our main focus is on understanding the structure and function of the large eIF3 complex. This is the most complicated initiation factor involved in mammalian protein synthesis, consisting of 13-protein subunits (800kDa). It plays a central role, acting on both protein synthesis initiation and termination, yet the molecular details of its many activities remain a mystery. We are interested in how this initiation factor promotes mRNA recruitment to the ribosome and subsequent initiation codon recognition. The eIF3 complex has also been suggested to possess many other binding partners, including protein kinases, interferon induced proteins, nonsense mediated decay components and viral proteins. Our long-term goal is to understand how this initiation factor acts as a scaffold to coordinate the functions of these other proteins on ribosome activity. Our approach is to combine techniques in structural biology with biochemistry and cell biology in order to answer these questions.
Laboratory Personnel:
327 Briggs Hall - Nancy Villa, BMB Graduate Student; Ali Ozes, Junior Specialist; Angelie Do; Junior Specialist; Trang Huynh, Undergraduate; James Neary, Undergraduate; Gao Chong, Undergraduate.