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Etude structurale des protéines du complexe réplicatif du virus de la rougeole

Abstract : Measles virus is a negative-strand RNA virus, member of the family Paramyxoviridae. Its replicative complex is composed of three main viral proteins : the RNA-dependent RNA polymerase (L), the nucleoprotein (N) and the phosphoprotein (P). This thesis presents a structural study, using biochemical and biophysical methods, of the phosphoprotein and of the nucleoprotein produced in the bacteria Escherichia coli. I have studied the regions involved in the polymerisation of N and identified a variant of interest for the study of N using X-ray crystallography. I have also set up the purification of a complex of N and P, a prelude to its structural study. Besides, I have shown that the N-terminal moiety of P is intrinsically disordered. I was able to extend this result to the P proteins of numerous related virus using biocomputing methods. Then, I have demonstrated the importance of structural disorder within the replicative complex of Paramyxoviridae (both from a functional point of view and because of its abundance). Beyond their immediate practical interest, these results indicate that the replicative machinery of these viruses might constitute a model system for the study of structural disorder in proteins. Furthermore, they raise numerous questions, and command a rethink of our vision of the replicative complex of these viruses, the study of which has a major importance in human health.
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https://tel.archives-ouvertes.fr/tel-00625114
Contributor : David Karlin <>
Submitted on : Tuesday, September 20, 2011 - 5:41:01 PM
Last modification on : Friday, December 4, 2020 - 3:09:29 AM
Long-term archiving on: : Wednesday, December 21, 2011 - 2:25:08 AM

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  • HAL Id : tel-00625114, version 1

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David Karlin. Etude structurale des protéines du complexe réplicatif du virus de la rougeole. Biochimie [q-bio.BM]. Université de la Méditerranée - Aix-Marseille II, 2002. Français. ⟨tel-00625114⟩

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