Modular Organization of Rabies Virus Phosphoprotein |
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Authors: | Francine C.A. Gerard,Euripedes de Almeida Ribeiro Jr,Cé dric Leyrat,Danielle Blondel,Rob W.H. Ruigrok |
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Affiliation: | 1 UJF-EMBL-CNRS UMI 3265 - Unit of Virus Host Cell Interactions, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France 2 Laboratoire de Virologie Moléculaire et Structurale, UMR 2472 CNRS-1157 INRA Bât. 14B, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France 3 Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Universités Aix-Marseille I et II, Case 932, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France |
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Abstract: | A phosphoprotein (P) is found in all viruses of the Mononegavirales order. These proteins form homo-oligomers, fulfil similar roles in the replication cycles of the various viruses, but differ in their length and oligomerization state. Sequence alignments reveal no sequence similarity among proteins from viruses belonging to the same family. Sequence analysis and experimental data show that phosphoproteins from viruses of the Paramyxoviridae contain structured domains alternating with intrinsically disordered regions. Here, we used predictions of disorder of secondary structure, and an analysis of sequence conservation to predict the domain organization of the phosphoprotein from Sendai virus, vesicular stomatitis virus (VSV) and rabies virus (RV P). We devised a new procedure for combining the results from multiple prediction methods and locating the boundaries between disordered regions and structured domains. To validate the proposed modular organization predicted for RV P and to confirm that the putative structured domains correspond to autonomous folding units, we used two-hybrid and biochemical approaches to characterize the properties of several fragments of RV P. We found that both central and C-terminal domains can fold in isolation, that the central domain is the oligomerization domain, and that the C-terminal domain binds to nucleocapsids. Our results suggest a conserved organization of P proteins in the Rhabdoviridae family in concatenated functional domains resembling that of the P proteins in the Paramyxoviridae family. |
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Keywords: | RV, rabies virus VSV, vesicular stomatitis virus SV, Sendai virus MNV, Mononegavirales N, nucleoprotein P, phosphoprotein M, matrix protein G, glycoprotein L, RNA-dependent RNA polymerase aa, amino acid(s) CTD, C-terminal domain SEC, size-exclusion chromatography MALLS, multi-angle laser light-scattering RI, refractometry |
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