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Title: Structural studies of the 30S ribosomal subunit
Author: Carter, A. P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Abstract:
Over the past three years, several groups have used x-ray crystallography to determine high-resolution atomic structures of the 30S and 50S subunits as well as a lower resolution structure of the whole ribosome. This explosion of structural information has allowed detailed questions about the molecular basis for ribosome function to be asked for the first time. This thesis begins with a description of the author's role as part of a team that determined a crystal structure of the 30S subunit from the thermophilic eubacterium Thermus thermophilus. The following three sections concern the structure of the 30S subunit solved in the presence of three antibiotics (paromomycin, streptomycin and spectinomycin). Each of these antibiotics provided insights into the mechanism of the ribosome. Paromomycin reduces the accuracy of translation, by increasing the affinity of incorrect transfer RNAs (tRNAs) for a given mRNA codon. The structure showed that paromomycin perturbs the structure of two rRNA bases (A1492, A1493) and provided the first good model for how these bases could monitor the interaction of a tRNA with an mRNA codon. Streptomycin also affects ribosomal accuracy. Its position suggested this effect might be the result of interfering with the movement of shoulder and platform domains of the 30S with respect to each other. The structure of a mutant ribosome, dependent on streptomycin, was solved in an attempt to clarify how this movement is important, but showed a structure similar to the wild type thus limiting the conclusions that could be drawn. Spectinomycin hinders the translocation of tRNAs through the ribosome. Its position, close to the hinge point of the head domain, led to a model in which it interferes with head movement. The final section of the thesis describes the structure of the 30S subunit in complex with a small initiation factor (IF1). The conformational changes observed on binding suggested a model for how IF1 could affect the interaction of the 30S and 50S subunits.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597340  DOI: Not available
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