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Theses

Etude structurale de la Nucléoprotéine du virus de la rage

Abstract : Rabies virus, a member of the Mononegavirales family, constitutes a serious health problem in developing
countries lacking effective vaccination programs. The genome of negative-strand RNA viruses is compacted
by the nucleoprotein (N) resulting in an N-RNA complex forming a tight helical nucleocapsid that is
packaged into enveloped virions. Transcription and replication in the cytoplasm upon virus infection requires
the N-RNA as a template for the RNA dependent RNA-polymerase complex. When N is expressed in insect
cells in the absence of the other viral proteins, the protein binds to cellular RNA molecules and ring-shaped
N-RNA complexes are produced. These rings are made up of 9 to 15 nucleoproteins subunits. We have been
able to separate these distinct size classes and crystallised the complex containing 11 N-protomers and an
RNA molecule of 99 ribonucleotides. The crystals diffracted to a resolution of 3.5 Å. The nucleoprotein
subunit is composed of two domains that clamp around the RNA at their interface and shield it off from the
environment, representing the replication inactive N-RNA conformation of the nucleocapsid inside the virus
particle. Polymerisation of the nucleoprotein protomers is achieved by domain exchange between monomers
acting as two hinges. The flexibility allowed by these hinges permits the formation of long N-RNA
complexes adopting the larger helical radius required for nucleocapsid formation. The sequestering of the
RNA within N indicates that the RNA has to dissociate from a monomer to become a template for the
polymerase complex. Other negative-strand RNA viruses such as filoviruses, paramyxoviruses, borna viruses
and influenza viruses may use the same structural principles to assemble a helical nucleocapsid. The
nucleoprotein is an interesting target for drug design as it only exists in viruses. This thesis also contains the
first experiments describing the characterization of the binding of the phosphoprotein, the polymerase cofactor,
to the N-RNA complex.
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Contributor : Aurélie Albertini <>
Submitted on : Friday, June 1, 2007 - 5:13:13 PM
Last modification on : Tuesday, November 24, 2020 - 1:38:02 PM
Long-term archiving on: : Thursday, April 8, 2010 - 6:43:51 PM

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  • HAL Id : tel-00151191, version 1

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Citation

Aurélie Albertini. Etude structurale de la Nucléoprotéine du virus de la rage. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00151191⟩

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