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Study of translation initiation factors eIF5B and eIF3

Laurent Guillon
Abstract : Translation initiation plays a central role in every living organism. Studying the proteins helping the ribosome toward this task, Initiation Factors (Ifs), allows to get insights into the complex molecular mechanisms ensuring a high fidelity and efficiency of translation initiation. When comparing the existing initiation factors in the three kingdoms of life, three universally conserved initiation factors were identified. Among these, the eukaryotic/archaeal factor e/aIF5B, the counterpart of the bacterial factor IF2, stimulates the ribosomal subunits joining step as in Bacteria. However, the universality of this factor was limited by the lack of reported interaction between the factor e/aIF5B and the initiator tRNA whereas such an interaction was characterized in Bacteria. A first part of this thesis work aimed at extending the functional similarity between the factors by bringing to light a binding of methionylated initiator tRNA by the factor e/aIF5B. The characteristics of this binding are very similar to the binding of formylated methionylated initiator tRNA by the bacterial factor IF2. A second part of my thesis work dealt with the factor eIF3, the most complex factor of the eukaryotic translation initiation apparatus. This multimeric factor, composed of 13 subunits in human and 5 in budding yeast, has no counterpart in the other kingdoms of life despite a central and essential role in Eukaryotes. In addition, eIF3 is involved in numerous cancers. However, the understanding of its functions is severely limited by the lack of structural information on subunits interactions and on interactions with other partners of the translation apparatus. This work led to the development of a plasmid library allowing the coexpression of Saccharomyces cerevisiae eIF3's subunits or stabilized forms of them in the Bacteria Escherichia coli. The purifications of the individual subunits and different subcomplexes are leading us on the road of the factor structure determination by an approach combining crystallography and electron microscopy.
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https://pastel.archives-ouvertes.fr/pastel-00004650
Contributor : Ecole Polytechnique <>
Submitted on : Wednesday, July 15, 2009 - 8:00:00 AM
Last modification on : Tuesday, June 30, 2015 - 11:05:35 AM

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Laurent Guillon. Study of translation initiation factors eIF5B and eIF3. Life Sciences [q-bio]. Ecole Polytechnique X, 2008. English. ⟨pastel-00004650⟩

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