Wayne State University

Aim Higher



College of Liberal Arts & Sciences
Department of Chemistry
Faculty Page
 
Tamara L. Hendrickson
Title Associate Professor
Division Biochemistry
Education B. A., Wellesley College, 1990
Ph.D., California Institute of Technology, 1996
NIH Postdoctoral Fellow, Massachusetts Institute of Technology, 1996-1997
NIH Postdoctoral Fellow, The Scripps Research Institute, 1997-2000
Office Chem 365
Phone (313)577-6914
E-Mail
Group http://chem.wayne.edu/hendrickson


Our research group uses a multidisciplinary approach to investigate two different aspects of protein biosynthesis and modification - Indirect tRNA aminoacylation pathways in Helicobacter pylori and fungal GPI membrane anchoring of proteins. We draw on techniques from biochemistry, organic and biophysical chemistry, and molecular and microbiology in order to understand these complex macromolecular processes.

GPI Membrane Anchoring of Proteins
Glycosylphosphatidylinositol (GPI) membrane anchors are complex glycolipids that are post-translationally attached to the C-termini of as many as 1% of eukaryotic proteins. Upon anchor attachment, these modified proteins are translocated to the outer cell wall where they play a variety of important cell surface functions. Our group investigates GPI transamidase (GPI-T), the enzyme that attaches GPI anchors to proteins. GPI-T is a complex enzyme, comprised of at least five subunits, all of which are membrane-bound.

We are interested in the characterization of GPI-T, both in vivo and in vitro. We are developing new tools to study this enzyme and new methodologies for its solubilization. We also seek to minimize GPI-T into a soluble enzyme that can be used to modifiy protein substrates with non-natural compounds of biophysical importance.

Indirect tRNA Aminoacylation
There are twenty proteinaceous amino acids that are commonly used by all organisms. In most cases, including humans, yeast, and E. coli, there are twenty aminoacyl-tRNA synthetases, with one enzyme responsible for attaching each encoded amino acid to the correct tRNA(s). However, in many organisms glutaminyl-tRNA synthetase and asparaginyl-tRNA synthetase (GlnRS and AsnRS, respectively) are missing. In these cases, the corresponding aminoacyl-tRNAs, Gln-tRNAGln and Asn-tRNAAsn, are made indirectly via transamidation of Glu-tRNAGln and Asp-tRNAAsn. This biosynthetic pathway requires the presence of two misacylating AARSs and a glutamine-dependent amidotransferase (Adt).

We are investigating the indirect biosynthesis of Gln-tRNAGln and Asn-tRNAAsn in the pathogenic bacterium Helicobacter pylori. H. pylori is missing both glutaminyl-tRNA synthetase and asparaginyl-tRNA synthetase. We are interested in understanding the evolution of direct versus indirect tRNA aminoacylation pathways as well as the mechanisms that are used by H. pylori to prevent misacylated tRNAs from entering the ribosome prior to conversion to their accurately aminoacylated counterpoints.








REPRESENTATIVE PUBLICATIONS

Cathopoulis, T. J.; Chuawong, P.; Hendrickson, T. L., "Conserved discrimination against misacylated tRNAs by two mesophilic elongation factor TU orthologs." Biochemistry, 2008, 7610-7616.

Meitzler, J. L.; Gray, J. J.; Hendrickson, T. L. "Truncation of the caspase-related subunit (Gpi8p) of Saccharomyces cerevisiae GPI transamidase: dimerization revealed." Arch. Biochem. Biophys., 2007, 462, 83-93.

Chuawong, P.; Hendrickson, T. L. "The nondiscriminating aspartyl-tRNA synthetase from Helicobacter pylori: anticodon-binding domain mutations that impact tRNA specificity and heterologous toxicity." Biochemistry, 2007, 45, 8079-8087.

Lee, J.; Hendrickson, T. L. "Divergent anticodon recognition in contrasting glutamyl-tRNA synthetases." J. Mol. Biol. 2004, 344, 1167-1174.

Skouloubris, S.; Ribas de Pouplana, L.; de Reuse, H.; Hendrickson, T. L. "A Non-cognate aminoacyl-tRNA synthetase that may resolve a missing link in protein evolution." Proc. Natl. Acad. Sci. USA, 2003, 100, 11297-11303.

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