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Paul D. Gershon
1222 Natural Sciences 1 -- 1413 Natural Sciences 1
Mail Code: 3900
Irvine, CA 92697
PHONE:
(949) 824-9606, 7954
FAX:
(949) 824-8551
E-MAIL:
pgershon@uci.edu
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Paul D. Gershon |
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Professor, Molecular Biology and Biochemistry School of Biological Sciences |
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Ph.D., University of Liverpool, 1985, Biochemistry |
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Research Interests
Nucleic acid-protein interactions and molecular dynamics, catalytic mechanisms, proteomics, virion structure
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Graduate Programs: Structural Biology and Molecular Biophysics Virology |
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Abstract I am currently funded to investigate the structure and molecular dynamics of poly(A) polymerase (PAP), using the vaccinia virus enzyme as a model. The vaccinia PAP was the first PAP for which a gene was identified (by the P.I.), and we are now close to having a three-dimensional structure. Vaccinia PAP is the only known polymerase that can translocate independently on single-stranded nucleic acid. How does it do this on a non-rigid polymer? Come to my lab and solve the mystery. I am also funded to investigate the catalytic mechanism of RNA O-methylation. Vaccinia protein VP39 provided the first three-dimensional structure for any poxvirus protein and any RNA methyltransferase (done collaboratively between the lab of the P.I. and Flor Quiocho, Baylor College of Medicine). The structure was then solved again, with bound RNA substrate and cofactor. Using various chemical biological and NMR techniques, we have elucidated aspects of its catalytic mechanism from hypotheses arising from the three-dimensional structure. My lab is responsible for a nascent proteomics mass spectrometry core facility, containing a MALDI-TOF/TOF and slated to contain an LC-ion trap MS plus peripherals. A collaboration between my lab and that of Dr. Alex McPherson (MB&B) has led to the clearest images obtained thus far of unprocessed vaccinia virions and subviral assemblies, providing a unique opportunity to identify viral proteins and functions present in various subviral assemblies. A collaboration between my lab and that of Dr. Phil Felgner provides an opportunity to characterize the vaccinia virus interactone based on the cloned whole proteome of vaccinia. |
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Other Experience |
| Updated: Last Updated: 07/06/2005 |
Gershon, P. D. and Khilko, S. N. 1995. Stable chelating linkage for reversible immobilization of oligohistidine tagged proteins in the BIAcore Surface Plasmon Resonance detector. J. Immunol. Methods 183, 65-76.
Hodel, A.E., Gershon, P.D., Shi, X. and Quiocho, F.A. 1996. The 1.85 Å structure of vaccinia protein VP39: A bifunctional enzyme that participates in the modification of both mRNA ends. Cell 85, 247-256.
Deng, L. and Gershon, P.D. 1997. Interplay of two uridylate-specific RNA binding sites in the translocation of poly(A) polymerase from vaccinia virus. EMBO J. 16(5), 1103-1113.
Hodel, A.E., Gershon, P.D., Shi, X., Wang, S-M. and Quiocho, F.A. 1997. Specific protein recognition of an mRNA cap through its alkylated base. Nature Structural Biology 4(5), 350-354.
Shi, X., Bernhardt, T.G., Wang, S-M. and Gershon, P.D. 1997. The surface region of the bifunctional vaccinia RNA modifying protein VP39 that interfaces with poly(A) polymerase is remote from the RNA binding cleft used for its mRNA 5’ cap methylation function. J. Biol. Chem. 272(37), 23292-23302
Hodel, A. E., Gershon, P. D., and Quiocho, F. A. 1998. Structural basis for sequence non-specific recognition of 5' capped mRNA by a cap-modifying enzyme. Molecular Cell 1(3), 443-447.
Lockless, S., Cheng, H.-T., Hodel, A.E., Quiocho, F.A. and Gershon, P.D. 1998. Recognition of capped RNA substrates by VP39, the vaccinia virus-encoded mRNA cap-specific 2’-O-methyltransferase. Biochemistry 37(23), 8564-8574.
Hodel, A. E., Quiocho, F. A. and Gershon, P. D. 1999. VP39 – an mRNA cap-specific 2'-O-methyltransferase. In: Structure and function of AdoMet-dependent methyltransferases. X. Cheng, R. M. Blumenthal, Eds. World Scientific Publishing Co./Imperial College Press.
Hu, G., Gershon, P.D., Hodel, A.E. and Quiocho, F.A. 1999. mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic sidechains. Proc. Natl. Acad. Sci. 96(13), 7149-7154.
Quiocho, F.A., Hu, G. and Gershon, P.D. 2000. Structural basis for mRNA cap recognition by proteins. Current Opinion in Structural Biology. 10(1), 78-86.
Gershon. P.D. 2000. (A)-tail of two polymerase structures (News & Views). Nature Structural Biology, 7(10), 819-821.
Peng, Z-H., Sharma, V., Singleton, S. and Gershon, P.D. 2002. Synthesis and application of a chain-terminating dinucleotide mRNA cap analog. Org. Lett., 4(2), 161-164.
Oguro, A., Johnson, L. and Gershon, P.D. 2002. Path of an RNA Ligand around the Surface of the Vaccinia VP39 Subunit of Its Cognate VP39-VP55 Protein Heterodimer. Chemistry & Biology 9(6), 679-690.
Malkin, A.J. McPherson, A. and Gershon, P.D. 2003. Structure of intracellular mature vaccinia virus visualized by in situ atomic force microscopy. J. Virol. 77(11), 6332-40.
Johnson, L., Liu, S. and Gershon, P.D. 2004. Molecular flexibility and discontinuous translocation of a non-templated polymerase. Journal of Molecular Biology 337(4), 843-885.
Li, C., Xia, Y., Gao, L. and Gershon, P.D. 2004. Mechanism of RNA 2'-O-methylation: Evidence that the catalytic lysine acts to steer rather than deprotonate the target nucleophile. Biochemistry 43(19), 5680-5687.
