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Structural studies of regulators of protein expression

In most species, highly sophisticated global regulatory networks regulate the expression of genes in response to environmental and physiological demands. The mechanisms devised control virtually every event involved in transcription and translation, as well as influencing mRNA degradation, protein stability, protein localization, protein-protein interactions, and protein function. In order to understand the general mechanism used by several organisms to control gene expression, three regulatory proteins were investigated using nuclear magnetic resonance (NMR) techniques. The systems studied were proteins involved in the control of gene expression at the transcriptional (YaeO, Chapter 2), posttranscriptional (CsrA, Chapter 3) and translational levels (aIF2Pbeta Chapter 4). / YaeO is a protein involved in the regulation of Rho-dependent transcription termination in bacteria. The solution structure of YaeO was solved, the first for a Rho inhibitor, and it was demonstrated that that YaeO binds to the primary RNA binding domain of Rho. This study suggests that YaeO inhibits transcription termination by blocking the primary RNA binding site in Rho. / The carbon storage regulator A from E. coli is a protein involved in the post-transcriptional control of numerous genes involved in carbohydrate metabolism in bacteria. It has been shown that CsrA prevents translation of its target mRNA by blocking access to the ribosome binding site. The binding studies, together with the structure of CsrA, reveal the potential RNA binding region. A model for CsrA recognition of its target mRNAs is also proposed. / The last section focuses on the archaeal translation initiation factor IF2beta. This protein is a key regulator of overall protein synthesis. The structure of aIF2beta was solved and bound zinc was proved to be necessary for the structural integrity of this translation factor. The function of aIF2beta in translation initiation was rationalized in terms of its structure and available structural data for translation factors aIF2alpha and aIF2gamma.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85912
Date January 2005
CreatorsGutierréz, Pablo, 1977-
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Department of Biochemistry.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 002261196, proquestno: AAINR21649, Theses scanned by UMI/ProQuest.

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