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ÉTUDE STRUCTURALE DES PROTÉINES DE LA CAPSIDE DE L'ADÉNOVIRUS

Abstract : Adenoviruses are dsDNA non enveloped icosahedral viruses. Although these viruses are widely studied in the area of gene therapy applications, the lack of fundamental knowledge especially from a structural point of view is probably partly responsible for the limited success of the first trials. As a part of a global structural study of adenoviral proteins, we focused on minor proteins, and particularly on protein IX. 4 trimers of protein IX are found at the center of each face of the capsid. Cryo-electron microscopy 3D reconstructions of human adenovirus in complex with Fabs directed against the protein IX C-terminal region, and a canine adenovirus where the C-terminal domain of protein IX was marked with GFP, enabled us to localise the C-terminal region at the capsid surface. A combination of these results with biophysical analyses of various mutants of protein IX allowed to propose a model of integration of this protein into the capsid surface. In particular we showed that protein IX forms a lattice between the different capsomers.
Our work also focused on another structural protein, the short fiber head of avian adenovirus. We solved the crystallographic structure of this protein at 2 Å resolution and compared it with other known fiber head structures. Inspite of a low sequence homology, the tertiary and quaternary structures of fiber heads are conserved within members of the adenovirus family. A phylogenetic tree based on the atomic structures of fiber heads revealed a new link between adenoviruses infecting different species. The structure also allowed us to emit hypotheses on the nature of cellular receptors for avian adenovirus.
The third structural protein we took an interest in is human adenovirus type 3 penton base. 12 copies of this pentameric protein further assemble into a highly symmetrical dodecahedron particle. The 80 Å cavity of the dodecahedrons and their ability to enter cells prompted to propose these assemblies as potential gene transfer vehicles for gene therapy. We recently succeeded to improve dodecahedron crystals to obtain X-ray diffraction up to 3.5 Å resolution. The structure of the assembly is being solved.
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Contributor : Majida El Bakkouri <>
Submitted on : Thursday, March 19, 2009 - 10:19:22 PM
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Majida El Bakkouri. ÉTUDE STRUCTURALE DES PROTÉINES DE LA CAPSIDE DE L'ADÉNOVIRUS. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00369461⟩

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