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Caractérisations biophysiques et structurales du complexe de réplication des Rhabdoviridae

Abstract : Vesicular stomatitis virus (VSV) serves as a model for studying the multiplication of viruses (Mononegavirales), whereas rabies (RV) is still a serious health problem. VSV & RV genomes encode in particular the nucleoprotein (N) and the phosphoprotein (P). N binds to the viral genome forming an N-RNA complex that serves as a matrix for viral transcription and replication. P is a cofactor of the viral polymerase (L), and a chaperone of N. P binds to N-RNA (C-terminal domain) and to L (N-terminal domain), making a physical link between the viral genome and L. The stoechiometry, the structure and the exact functions of P oligomers are controversial or unknown. The aim of this work was to undertake a structural and biophysical characterization of P and of the complexes that it forms with N-RNA in order to understand the dynamic of the replicative complex of theses viruses.
Biophysical studies of RV & VSV P show that these proteins behave as elongated dimers in solution. Bioinformatics analysis indicates a modular organisation of P, confirmed with biochemical and biophysical datas of RV P mutants. Structure of the C-terminal domain of VSV P was solved by NMR showing a homology with the C-terminal domain of RV P. Characterization of the interaction between P and N-ARN rings complexes revealed two forms of N-RNA-P complexes, with one and 2 dimers of P. Structural analysis with electron microscopy of the nucleocapsid-P complexes revealed an important conformational change.
The viral genome must dissociate locally from N to allow the viral polymerase to access to the genome information. The N-RNA-P interaction is an interesting target for drug design as it only exists in viruses.
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https://tel.archives-ouvertes.fr/tel-00343710
Contributor : Francine Gerard <>
Submitted on : Tuesday, December 2, 2008 - 4:05:11 PM
Last modification on : Friday, December 11, 2020 - 2:58:03 PM

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  • HAL Id : tel-00343710, version 1

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Citation

Francine Gerard. Caractérisations biophysiques et structurales du complexe de réplication des Rhabdoviridae. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00343710⟩

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