title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication.
abstract: NTP-motif, a consensus sequence previously shown to be characteristic of numerous NTP-utilizing enzymes, was identified in nonstructural proteins of several groups of positive-strand RNA viruses. These groups include picorna-, alpha-, and coronaviruses infecting animals and como-, poty-, tobamo-, tricorna-, hordei-, and furoviruses of plants, totalling 21 viruses. It has been demonstrated that the viral NTP-motif-containing proteins constitute three distinct families, the sequences within each family being similar to each other at a statistically highly significant level. A lower, but still valid similarity has also been revealed between the families. An overall alignment has been generated, which includes several highly conserved sequence stretches. The two most prominent of the latter contain the socalled "A" and "B" sites of the NTP-motif, with four of the five invariant amino acid residues observed within these sequences. These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. In this group the "A" and "B" sites of the NTP-motif are the most conserved sequences and, by inference, should play the principal role in the functioning of the proteins. A hypothesis is proposed that all these proteins possess NTP-binding capacity and possibly NTPase activity, performing some NTP-dependent function in viral RNA replication. The importance of phylogenetic analysis for the assessment of the significance of the occurrence of the NTP-motif (and of sequence motifs of this sort in general) in proteins is emphasized.
authors.affiliation: Institute of Poliomyelitis, USSR Academy of Medical Sciences, Moscow Region.
authors.forename: A E
authors.initials: AE
authors.lastname: Gorbalenya
authors.forename: V M
authors.initials: VM
authors.lastname: Blinov
authors.forename: A P
authors.initials: AP
authors.lastname: Donchenko
authors.forename: E V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002213:Capsid / Q000235:genetics / Q000648:ultrastructure; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009711:Nucleotides / Q000378:metabolism*; D010802:Phylogeny; D012328:RNA Viruses / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics / Q000648:ultrastructure; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins / Q000235:genetics* / Q000648:ultrastructure; D014779:Virus Replication
chemical_list: D009711:Nucleotides; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins