Author

Andrew Hadd

Date

12-2014

Document Type

Dissertation

Degree Name

Ph.D.

Department

Department of Biochemistry and Molecular Biology

Institution

Oregon Health & Science University

Abstract

Translating nucleic acid based information into a protein product is at the heart of the genetic code. Aminoacyl-tRNA synthetases (aaRSs) function is the basis of decoding the genetic code by ligating the cognate tRNA and amino acid together. Given this role, aaRSs maintain an enormous level of specificity for their amino acid and tRNA substrates. This thesis sought to uncover the mechanisms of substrate specificity in aaRSs using glutaminyl- and glutamyl-tRNA synthetases (GlnRS and GluRS, respectively) as model systems. The work addresses the macromolecular coevolution in this subfamily, revealing the nucleic acid recognition signatures within the tRNA utilized by eukaryotic GlnRS and GluRS. Furthermore a rational engineering method discovered that the aforementioned tRNA signatures also assist the corresponding GlxRS in amino acid recognition, a novel concept in genetic code translation. These generalized principles and engineering strategy can be applied to further our understandings in proteinnucleic acid readout mechanisms as well as achieving goals in genetic code expansion for synthetic biology efforts.

Identifier

doi:10.6083/M4RX99TV

School

School of Medicine

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