Honors & Awards

  • NIH NRSA Postdoctoral Fellowship, NIGMS (2012-15)

Professional Education

  • Doctor of Philosophy, Northwestern University (2011)

Stanford Advisors

Research & Scholarship

Current Research and Scholarly Interests

Translational control of bacterial development


Journal Articles

  • Histidine 66 in Escherichia coli Elongation Factor Tu Selectively Stabilizes Aminoacyl-tRNAs JOURNAL OF BIOLOGICAL CHEMISTRY Chapman, S. J., Schrader, J. M., Uhlenbeck, O. C. 2012; 287 (2): 1229-1234


    The universally conserved His-66 of elongation factor Tu (EF-Tu) stacks on the side chain of the esterified Phe of Phe-tRNA(Phe). The affinities of eight aminoacyl-tRNAs were differentially destabilized by the introduction of the H66A mutation into Escherichia coli EF-Tu, whereas Ala-tRNA(Ala) and Gly-tRNA(Gly) were unaffected. The H66F and H66W proteins each show a different pattern of binding of 10 different aminoacyl-tRNAs, clearly showing that this position is critical in establishing the specificity of EF-Tu for different esterified amino acids. However, the H66A mutation does not greatly affect the ability of the ternary complex to bind ribosomes, hydrolyze GTP, or form dipeptide, suggesting that this residue does not directly participate in ribosomal decoding. Selective mutation of His-66 may improve the ability of certain unnatural amino acids to be incorporated by the ribosome.

    View details for DOI 10.1074/jbc.M111.294850

    View details for Web of Science ID 000299170300038

    View details for PubMedID 22105070

  • Is the sequence-specific binding of aminoacyl-tRNAs by EF-Tu universal among bacteria? NUCLEIC ACIDS RESEARCH Schrader, J. M., Uhlenbeck, O. C. 2011; 39 (22): 9746-9758


    Three base pairs in the T-stem are primarily responsible for the sequence-specific interaction of tRNA with Escherichia coli and Thermus thermophilus EF-Tu. While the amino acids on the surface of EF-Tu that contact aminoacyl-tRNA (aa-tRNA) are highly conserved among bacteria, the T-stem sequences of individual tRNA are variable, making it unclear whether or not this protein-nucleic acid interaction is also sequence specific in other bacteria. We propose and validate a thermodynamic model that predicts the ?G° of any tRNA to EF-Tu using the sequence of its three T-stem base pairs. Despite dramatic differences in T-stem sequences, the predicted ?G° values for the majority of tRNA classes are similar in all bacteria and closely match the ?G° values determined for E. coli tRNAs. Each individual tRNA class has evolved to have a characteristic ?G° value to EF-Tu, but different T-stem sequences are used to achieve this ?G° value in different bacteria. Thus, the compensatory relationship between the affinity of the tRNA body and the affinity of the esterified amino acid is universal among bacteria. Additionally, we predict and validate a small number of aa-tRNAs that bind more weakly to EF-Tu than expected and thus are candidates for acting as activated amino acid donors in processes outside of translation.

    View details for DOI 10.1093/nar/gkr641

    View details for Web of Science ID 000298186000030

    View details for PubMedID 21893586

  • Tuning the affinity of aminoacyl-tRNA to elongation factor Tu for optimal decoding PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Schrader, J. M., Chapman, S. J., Uhlenbeck, O. C. 2011; 108 (13): 5215-5220


    To better understand why aminoacyl-tRNAs (aa-tRNAs) have evolved to bind bacterial elongation factor Tu (EF-Tu) with uniform affinities, mutant tRNAs with differing affinities for EF-Tu were assayed for decoding on Escherichia coli ribosomes. At saturating EF-Tu concentrations, weaker-binding aa-tRNAs decode their cognate codons similarly to wild-type tRNAs. However, tighter-binding aa-tRNAs show reduced rates of peptide bond formation due to slow release from EF-Tu•GDP. Thus, the affinities of aa-tRNAs for EF-Tu are constrained to be uniform by their need to bind tightly enough to form the ternary complex but weakly enough to release from EF-Tu during decoding. Consistent with available crystal structures, the identity of the esterified amino acid and three base pairs in the T stem of tRNA combine to define the affinity of each aa-tRNA for EF-Tu, both off and on the ribosome.

    View details for DOI 10.1073/pnas.1102128108

    View details for Web of Science ID 000288894800020

    View details for PubMedID 21402928

  • Understanding the Sequence Specificity of tRNA Binding to Elongation Factor Tu using tRNA Mutagenesis JOURNAL OF MOLECULAR BIOLOGY Schrader, J. M., Chapman, S. J., Uhlenbeck, O. C. 2009; 386 (5): 1255-1264


    Measuring the binding affinities of 42 single-base-pair mutants in the acceptor and T Psi C stems of Saccharomyces cerevisiae tRNA Phe to Thermus thermophilus elongation factor Tu (EF-Tu) revealed that much of the specificity for tRNA occurs at the 49-65, 50-64, and 51-63 base pairs. Introducing the same mutations at the three positions into Escherichia coli tRNA CAG Leu resulted in similar changes in binding affinity. Swapping the three pairs from several E. coli tRNAs into yeast tRNA Phe resulted in chimeras with EF-Tu binding affinities similar to those for the donor tRNA. Finally, analysis of double- and triple-base-pair mutants of tRNA Phe showed that the thermodynamic contributions at the three sites are additive, permitting reasonably accurate prediction of the EF-Tu binding affinity for all E. coli tRNAs. Thus, it appears that the thermodynamic contributions of three base pairs in the T Psi C stem primarily account for tRNA binding specificity to EF-Tu.

    View details for DOI 10.1016/j.jmb.2009.01.021

    View details for Web of Science ID 000264383500007

    View details for PubMedID 19452597

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