Abstract/Details

The molecular basis for high fidelity tRNA selection on the ribosome


2006 2006

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Abstract (summary)

Faithful translation of a messenger RNA (mRNA) into a polypeptide chain depends largely on the specificity with which the cognate aminoacyl tRNA (aa-tRNA) is selected during each round of protein chain elongation on the ribosome. The mechanism by which high-fidelity tRNA selection is achieved is complex, as it needs to account for high specificity as well as for high speed. Previous work has shown that an induced fit mechanism provides the required discrimination power. This mechanism involves a series of conformational changes induced only by the cognate aa-tRNA that result in selective acceleration of critical steps during the decoding process for the cognate but not for an incorrect aa-tRNA. The nature of the required conformational changes is not yet fully understood. By kinetically characterizing a variant tRNATrp we identified the body of the tRNA itself as a critical player in this selective rate acceleration, and thus as a critical component of the induced fit mechanism. We have also studied the contribution of conserved residues in the decoding site of the ribosome by carrying out a mutational analysis. Our results show that these nucleotides are essential for cognate aa-tRNA selection. In addition, we carried out a biochemical epistasis analysis combining these variant ribosomes with the mutant tRNATrp and antibiotics that are known to promote miscoding. These studies revealed at least two requirements for tRNA selection on the ribosome, which further experiments will help to define. Together, the results presented in this thesis increase our understanding of the molecular basis for high-fidelity decoding during protein synthesis on the ribosome.

Indexing (details)


Subject
Molecular biology;
Biophysics
Classification
0307: Molecular biology
0786: Biophysics
Identifier / keyword
Biological sciences; Protein synthesis; Ribosome; tRNA
Title
The molecular basis for high fidelity tRNA selection on the ribosome
Author
Cochella, Luisa
Number of pages
158
Publication year
2006
Degree date
2006
School code
0098
Source
DAI-B 67/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780542643132
Advisor
Green, Rachel
University/institution
The Johns Hopkins University
University location
United States -- Maryland
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3213681
ProQuest document ID
305317754
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305317754
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