Mechanistic and bioinformatic studies of mitochondrial ribosomes and auxiliary translational factors Public Deposited

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  • March 21, 2019
  • Grasso, Domenick Gabriel
    • Affiliation: College of Arts and Sciences, Department of Chemistry
  • This body of work is focused on mitochondrial translational systems. This apparatus synthesizes vital components of the electron transport chain facilitating the production of energy in eukaryotic cells. Of particular interest is the role of mammalian mitochondrial initiation factor 2 (IF2mt) in this process. This factor recruits the initiatior fMet-tRNA to begin protein synthesis within this organelle. IF2mt is unique in that it possesses an insertion. The work described here demonstrates that the insertion acts as the factor equivalent of initiation factor 1 (IF1). IF1 is an essential gene in prokaryotes and eukaryotes (eIF1A) but has yet to be discovered in mitochondria. IF2mt is a GTPase and the guanine ring binding region in this factor was probed to determine the effect of mutations on the X residue of the guanine ring binding motif NKXD. Quite surprisingly despite the connotation of X being random, this residue is very sensitive to perturbation. Other work included in this dissertation includes a bioinformatics analysis of the proteins found in a Leishmania tarentolae mitochondrial ribosomal small subunit particle. L. tarentolae is a member of the trypanosomitids family, whose members are known to cause African sleeping sickness and South American Chagas disease. Examination of this organism offers a deeper understanding to the mechanism of action of these disease causing organisms and offers the potential development of therapies for these illnesses. This study explored the limitations of “hits” produced by search algorithms as well as insight into mitochondrial ribosomal protein evolution. This last chapter of this dissertation attempts to further the understanding of the mechanisms of translation in the mammalian mitochondria by probing for previously unknown translational factors. Multiple approaches are employed to find these factors including alignments to factors known to be involved in the prokaryotic translational apparatus, such as LepA, as well as promoter and import sequence analysis.
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  • Spremulli, Linda
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  • University of North Carolina at Chapel Hill
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