Boards, Advisory Committees, Professional Organizations


  • BD-STEP Fellow, VA Palo Alto (2017 - Present)

Professional Education


  • Master of Public Health, Univ Texas Health Science Ctr-Houston (2017)
  • Bachelor of Science, National Taiwan University (2007)
  • Master of Science, Univ Texas Health Science Ctr-Houston (2017)
  • Doctor of Philosophy, Rice University (2013)

Lab Affiliations


All Publications


  • Structure and Dynamics of the Tetra-A Loop and (A-A)-U Sequence Motif within the Coliphage GA Replicase RNA Operator BIOCHEMISTRY Chang, A. T., Tran, M., Nikonowicz, E. P. 2017; 56 (21): 2690–2700

    Abstract

    The three-dimensional structure of a RNA hairpin containing the RNA operator binding site for bacteriophage GA coat protein is presented. The phage GA operator contains the asymmetric (A-A)-U sequence motif and is capped by a four-adenine (tetra-A) loop. The uridine of the (A-A)-U motif preferentially pairs with the 5'-proximal cross-strand adenine, and the 3'-proximal adenine stacks into the helix. The tetra-A loop is well-ordered with adenine residues 2-4 forming a 3' stack. This loop conformation stands in contrast to the structure of the 5'-AUUA loop of the related phage MS2 operator in which residues 1 and 2 form a 5' stack. The context dependence of the (A-A)-U sequence motif conformation was examined using structures of 76 unique occurrences from the Protein Data Bank. The motif almost always has one adenine bulged and the other adenine adopting an A-U base pair. In the case in which the (A-A)-U motif is flanked by only one Watson-Crick base pair, the adenine adjacent to the flanking base pair tends to bulge; 80% of motifs with a 3' flanking pair have a 3' bulged adenine, and 84% of motifs with a 5' flanking pair have a 5' bulged adenine. The frequencies of 3'- and 5'-proximal adenines bulging are 33 and 67%, respectively, when the (A-A)-U motif is flanked by base pairs on both sides. Although a 3' flanking cytidine correlates (88%) with bulging of the 5'-proximal adenine, no strict dependence on flanking nucleotide identity was identified for the 5' side.

    View details for PubMedID 28488852

  • Structure determination of noncanonical RNA motifs guided by (1)H NMR chemical shifts. Nature methods Sripakdeevong, P., Cevec, M., Chang, A. T., Erat, M. C., Ziegeler, M., Zhao, Q., Fox, G. E., Gao, X., Kennedy, S. D., Kierzek, R., Nikonowicz, E. P., Schwalbe, H., Sigel, R. K., Turner, D. H., Das, R. 2014; 11 (4): 413-416

    View details for DOI 10.1038/nmeth.2876

    View details for PubMedID 24584194

  • Solution NMR determination of hydrogen bonding and base pairing between the glyQS T box riboswitch Specifier domain and the anticodon loop of tRNA(Gly) FEBS LETTERS Chang, A. T., Nikonowicz, E. P. 2013; 587 (21): 3495–99

    Abstract

    In Gram-positive bacteria the tRNA-dependent T box riboswitch regulates the expression of many amino acid biosynthetic and aminoacyl-tRNA synthetase genes through a transcription attenuation mechanism. The Specifier domain of the T box riboswitch contains the Specifier sequence that is complementary to the tRNA anticodon and is flanked by a highly conserved purine nucleotide that could result in a fourth base pair involving the invariant U33 of tRNA. We show that the interaction between the T box Specifier domain and tRNA consists of three Watson-Crick base pairs and that U33 confers stability to the complex through intramolecular hydrogen bonding. Enhanced packing within the Specifier domain loop E motif may stabilize the complex and contribute to cognate tRNA selection.

    View details for DOI 10.1016/j.febslet.2013.09.003

    View details for Web of Science ID 000325978700020

    View details for PubMedID 24036450

    View details for PubMedCentralID PMC3834770

  • Solution Nuclear Magnetic Resonance Analyses of the Anticodon Arms of Proteinogenic and Nonproteinogenic tRNA(Gly) BIOCHEMISTRY Chang, A. T., Nikonowicz, E. P. 2012; 51 (17): 3662–74

    Abstract

    Although the fate of most tRNA molecules in the cell is aminoacylation and delivery to the ribosome, some tRNAs are destined to fulfill other functional roles. In addition to their central role in translation, tRNA molecules participate in processes such as regulation of gene expression, bacterial cell wall biosynthesis, viral replication, antibiotic biosynthesis, and suppression of alternative splicing. In bacteria, glycyl-tRNA molecules with anticodon sequences GCC and UCC exhibit multiple extratranslational functions, including transcriptional regulation and cell wall biosynthesis. We have determined the high-resolution structures of three glycyl-tRNA anticodon arms with anticodon sequences GCC and UCC. Two of the tRNA molecules are proteinogenic (tRNA(Gly,GCC) and tRNA(Gly,UCC)), and the third is nonproteinogenic (np-tRNA(Gly,UCC)) and participates in cell wall biosynthesis. The UV-monitored thermal melting curves show that the anticodon arm of tRNA(Gly,UCC) with a loop-closing C-A(+) base pair melts at a temperature 10 °C lower than those of tRNA(Gly,GCC) and np-tRNA(Gly,UCC). U-A and C-G pairs close the loops of the latter two molecules and enhance stem stability. Mg(2+) stabilizes the tRNA(Gly,UCC) anticodon arm and reduces the T(m) differential. The structures of the three tRNA(Gly) anticodon arms exhibit small differences among one another, but none of them form the classical U-turn motif. The anticodon loop of tRNA(Gly,GCC) becomes more dynamic and disordered in the presence of multivalent cations, whereas metal ion coordination in the anticodon loops of tRNA(Gly,UCC) and np-tRNA(Gly,UCC) establishes conformational homogeneity. The conformational similarity of the molecules is greater than their functional differences might suggest. Because aminoacylation of full-length tRNA molecules is accomplished by one tRNA synthetase, the similar structural context of the loop may facilitate efficient recognition of each of the anticodon sequences.

    View details for DOI 10.1021/bi201900j

    View details for Web of Science ID 000303349500015

    View details for PubMedID 22468768

    View details for PubMedCentralID PMC3361369