The rearrangement of motif F in the flavivirus RNA-directed RNA polymerase

Int J Biol Macromol. 2018 Mar:108:990-998. doi: 10.1016/j.ijbiomac.2017.11.009. Epub 2017 Nov 4.

Abstract

In the flavivirus genus, the non-structural protein NS5 plays a central role in RNA viral replication and constitutes a major target for drug discovery. One of the prime challenges in the study of NS5 protein is to investigate the interplay between the two protein domains, namely, the RNA-dependent RNA polymerase (RdRp) domain and the methyltransferase (MTase) domain. These investigations could clarify the multiple roles of NS5 protein in the virus life cycle. Here we present the results of sequence analyses and structural bioinformatics studies of NS5 protein, which suggest that the conserved motif F in the NS5 protein could act as a lock which controls the rearrangement of the domains and as a switch in the protein enzymatic activity.

Keywords: Flavivirus; Homology modeling; Molecular dynamics; Motif F; RNA-dependent RNA polymerase.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Flavivirus / enzymology
  • Flavivirus / genetics*
  • Gene Rearrangement*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Nucleotide Motifs*
  • Protein Conformation
  • Protein Domains
  • RNA-Dependent RNA Polymerase / chemistry*
  • RNA-Dependent RNA Polymerase / genetics*
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics

Substances

  • NS5 protein, flavivirus
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase