Two domains distantly related to protein-tyrosine kinases in the vesicular stomatitis virus polymerase.
We have carried out an exhaustive search for amino acid sequence similarities between vesicular stomatitis virus (VSV) proteins and database entries. Unexpectedly, we found that the L polymerase protein contains two blocks of sequence (residues 725-1102 and 1291-1671) with distant but statistically significant similarity to the catalytic domain of tyrosine-specific protein kinases. The first kinase-like region is most similar to members of the Abl subfamily, Fes and Fps (26.6% and 27.3% identity, respectively), whereas the second region is closest to members of the platelet-derived growth factor receptor (PDGFR) subfamily, PDGFR and Kit (30.4% and 25.9% identity, respectively). Multiple alignment of the catalytic domain of these kinases to all three rhabdovirus L protein sequences available (VSV Indiana, VSV New Jersey, and rabies) revealed that the polymerases contain many but not all residues well conserved in the protein kinase family. Similarity was highest for VSV Indiana and lowest for rabies. We conclude that the kinase-like regions in the rhabdoviral L proteins are probably very distantly related to the protein kinase family. The similarities could either reflect contemporary protein kinase activity or represent some other function(s) associated with these large multifunctional polymerase proteins. Our findings also shed new light on questions of the origins and evolution of RNA viruses.
McClure
M A
MA
Department of Biology, University of California San Diego 92093.
Perrault
J
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D012316:RNA Nucleotidyltransferases / Q000032:analysis*; D012324:RNA-Dependent RNA Polymerase / Q000032:analysis*; D014721:Vesicular stomatitis Indiana virus / Q000201:enzymology*; D018116:Vesiculovirus; D014764:Viral Proteins / Q000648:ultrastructure
D014764:Viral Proteins; D011505:Protein-Tyrosine Kinases; D012316:RNA Nucleotidyltransferases; D012324:RNA-Dependent RNA Polymerase