Article thumbnail

A Bioinformatics Approach to the Structure, Function, and Evolution of the Nucleoprotein of the Order Mononegavirales

By Sean B. Cleveland, John Davies and Marcella A. McClure


The goal of this Bioinformatic study is to investigate sequence conservation in relation to evolutionary function/structure of the nucleoprotein of the order Mononegavirales. In the combined analysis of 63 representative nucleoprotein (N) sequences from four viral families (Bornaviridae, Filoviridae, Rhabdoviridae, and Paramyxoviridae) we predict the regions of protein disorder, intra-residue contact and co-evolving residues. Correlations between location and conservation of predicted regions illustrate a strong division between families while high- lighting conservation within individual families. These results suggest the conserved regions among the nucleoproteins, specifically within Rhabdoviridae and Paramyxoviradae, but also generally among all members of the order, reflect an evolutionary advantage in maintaining these sites for the viral nucleoprotein as part of the transcription/replication machinery. Results indicate conservation for disorder in the C-terminus region of the representative proteins that is important for interacting with the phosphoprotein and the large subunit polymerase during transcription and replication. Additionally, the C-terminus region of the protein preceding the disordered region, is predicted to be important for interacting with the encapsidated genome. Portions of the N-terminus are responsible for N∶N stability and interactions identified by the presence or lack of co-evolving intra-protein contact predictions. The validation of these prediction results by current structural information illustrates the benefits of the Disorder, Intra-residue contact and Compensatory mutation Correlator (DisICC) pipeline as a method for quickly characterizing proteins and providing the most likely residues and regions necessary to target for disruption in viruses that have little structural information available

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1999). A neural network based predictor of residue contacts in proteins.
  2. (1991). Assembly and Transcription of Synthetic Vesicular Stomatitis Virus Nucleocapsids.
  3. (2001). Bayesian Inference of Phylogeny and Its Impact on Evolutionary Biology.
  4. (2006). Beilong virus, a novel paramyxovirus with the largest genome of non-segmented negative-stranded RNA viruses.
  5. (2006). CAPS: coevolution analysis using protein sequences.
  6. (2003). Chimeric pneumovirus nucleocapsid (N) proteins allow identification of amio acids essential for the function of the repiratory syncytial virus N protein.
  7. (1999). Coevolving protein residues: maximum likelihood identification and relationship to structure.
  8. (2004). Complete Genome Sequence of Fer-de-Lance Virus Reveals a Novel Gene in Reptilian Paramyxoviruses.
  9. (2004). ConSeq: the identification of functionally and structurally important residues in protein sequences.
  10. (2010). Endogenous non-retroviral RNA virus elements in mammalian genomes.
  11. (2009). Evolution of Teleost Fish Retroviruses: Characterization of New Retroviruses with Cellular Genes.
  12. (2003). Full-length genome sequence of Mossman virus, a novel paramyxovirus isolated from rodents in Australia.
  13. (2006). Functional mapping of the nucleoprotein of Ebola virus.
  14. (2011). Genomics and structure/function studies of Rhabdoviridae proteins involved in replication and transcription. Antiviral Research. In Press. Available at: http:// a598f9b575a7a052a7.
  15. (1998). Identification of a region of the rabies virus N protein involved in direct binding to the viral RNA.
  16. (1999). Identification of nucleocapsid protein residues required for Sendai virus nucleocapsid formation and genome replication.
  17. (1997). Improving contact predictions by the combination of correlated mutations and other sources of sequence information.
  18. (2009). In vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing HIV-1 Gag following intramuscular, intranasal, or intravenous inoculation.
  19. (1997). Initiation of vesicular stomatitis virus mutant polR1 transcription internally at the N gene in vitro.
  20. (2002). Intrinsically unstructured proteins.
  21. (2003). Investigations into the amino-terminal domain of the respiratory syncytial virus nucleocapsid protein reveal elements important for nucelocapsid formation and interaction with the phophoprotein.
  22. (1997). Isolation and Characterization of Vesicular Stomatitis Virus PolR Revertants: Polymerase Readthrough of the Leader-N Gene Junction Is Linked to an ATP-Dependent Function.
  23. (2005). IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content.
  24. (2009). Jalview Version 2–a multiple sequence alignment editor and analysis workbench.
  25. (2008). Mapping the Peste des Petits Ruminants virus nucleoprotein: Identification of two domains involved in protein self-association.
  26. (2004). Mapping the phosphoprotein binding site on Sendai virus NP protein assembled into nucleocapsids.
  27. (2001). Molecular Characterization of Menangle Virus, a Novel Paramyxovirus which Infects Pigs, Fruit Bats, and Humans.
  28. (2001). Molecular phylogenetics: state-of-the-art methods for looking into the past.
  29. (2007). MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.
  30. (2003). MrBayes 3: Bayesian phylogenetic inference under mixed models.
  31. (1992). Phosphorylation of specific serine residues within the acidic domain of the phosphoprotein of vesicular stomatitis virus regulates transcription in vitro.
  32. (1999). Predicting protein disorder for N-, C-, and internal regions.
  33. (2003). Protein Disorder Prediction: Implications for Structural Proteomics.
  34. (2004). Rabies virus nucleoprotein as a carrier for foreign antigens.
  35. (2007). Rambaut A
  36. (2010). Reassessing conflicting evolutionary histories of the Paramyxoviridae and the origins of respiroviruses with Bayesian multigene phylogenies.
  37. (2008). Recent developments in the MAFFT multiple sequence alignment program.
  38. (2004). Regions on nucleocapsid protein of Newcastle disease virus that interact with its phosphoprotein.
  39. (1994). Respiratory syncytial virus nucleocapsid protein (N) expressed in insect cells forms nucleocapsid-like structures.
  40. (2008). Role of Intermolecular Interactions of Vesicular Stomatitis Virus Nucleoprotein in RNA Encapsidation.
  41. (2001). Sequence complexity of disordered protein.
  42. (1997). Sequence data analysis for long disordered regions prediction in the calcineurin family.
  43. (2004). Structural basis for the attachment of a paramyxoviral polymerase to its template.
  44. (2007). Structural comparisons of the nucleoprotein from three negative strand RNA virus families.
  45. (2001). Structured disorder and conformational selection.
  46. (2001). Strucuture of Recombinant Rabie Virus Nucleoprotein-RNA Complex and Identification of the Phosphoprotein Binding site.
  47. (1989). The 1:1 N-NS Protein Complex of Vesicular Stomatitis Virus Is Essential for Efficient Genome Replication.
  48. (2004). The C-terminal domain of measles virus nucleoprotein belongs to the class of intrinsically disordered proteins that fold upon binding to their physiological partner.
  49. (1994). The nucleoprotein of Marburg virus is phosphorylated.
  50. (2005). The Pairwise Energy Content Estimated from Amino Acid Composition Discriminates between Folded and Intrinsically Unstructured Proteins.
  51. (2004). UCSF Chimera—A visualization system for exploratory research and analysis.
  52. (2006). Valencia A
  53. (1989). Vesicular Stomatitis Virus RNA Replication: a Role for the NS Protein.
  54. (2004). Vesicular stomatitis virus: reinventing the bullet.