Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus.
A sequence motif that is conserved in a number of S-adenosylmethionine (SAM)-utilizing methyltransferases and is implicated in SAM binding was identified in the N-terminal portion of NS5 proteins of flaviviruses and in lambda 2 protein of reovirus. An additional conserved motif was shared by these viral proteins and two distinct groups of methyltransferases including as the prototypes Rhodobacter capsulatus hydroxyneurosporene methylase (crtF gene product) and yeast 3,4-dihydroxy-5-hexaprenylbenzoate methylase (COQ3 gene product), respectively. Statistically significant similarity was revealed between the region of flavivirus NS5 containing the SAM-binding motif and a newly characterized family of putative methyltransferases from bacteria, yeast and plants, which is related to the Coq3 group. Amino acid sequence signatures were derived that are unique for NS5 proteins and different subsets of (putative) cellular methyltransferases. It is hypothesized that the N-terminal domain of NS5 is a methyltransferase involved in viral RNA capping. Thus NS5 may be a two-domain protein, with its C-terminal domain comprising the RNA-dependent RNA polymerase. The putative methyltransferase domain of flaviviruses is unrelated to the methyltransferase domain previously characterized in positive-strand RNA viruses of the alphavirus-like supergroup. The lack of sequence similarity and different location of the putative methyltransferase domain underscores the drastic difference in the genome layout of flaviviruses and alphaviruses. The identification of the putative methyltransferase domain in reovirus lambda 2 protein is compatible with the available evidence that this protein is the viral capping enzyme.
Koonin
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National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894.
D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D005416:Flavivirus / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012436:S-Adenosylmethionine / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D012436:S-Adenosylmethionine; D008780:Methyltransferases