PS50526

RdRp of negative ssRNA viruses with non-segmented genomes catalytic domain profile

PROSITE profiles entry
Member databasePROSITE profiles
PROSITE profiles typedomain
Short nameRDRP_SSRNA_NEG_NONSEG

Description

RNA-directed RNA polymerase (RdRp) (EC 2.7.7.48) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage
[3]
[4]
. It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear. The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product
[2]
. All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organization has been likened to the shape of a right hand with three subdomains termed fingers, palm and thumb
[1]
. Only the palm subdomain, composed of a four-stranded antiparallel beta-sheet with two alpha-helices, is well conserved among all of these enzymes. In RdRp, the palm subdomain comprises three well conserved motifs (A, B and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the Asp residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The Asn residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and thus determines whether RNA is synthesized rather than DNA
[5]
. RNA viruses with no DNA stage can be placed in three main categories based on their replication and coding strategies: positive single-stranded RNA (ssRNA), negative ssRNA and double-stranded RNA (dsRNA) viruses. To recognize RNA-directed RNA polymerase we have developed six profiles that roughly follow this classification (see below). They are all directed against the catalytic region (palm subdomain).

References

1.Structure of the RNA-dependent RNA polymerase of poliovirus. Hansen JL, Long AM, Schultz SC. Structure 5, 1109-22, (1997). View articlePMID: 9309225

2.De novo initiation of viral RNA-dependent RNA synthesis. Kao CC, Singh P, Ecker DJ. Virology 287, 251-60, (2001). View articlePMID: 11531403

3.Tentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases. Koonin EV, Gorbalenya AE, Chumakov KM. FEBS Lett. 252, 42-6, (1989). View articlePMID: 2759231

4.A reevaluation of the higher taxonomy of viruses based on RNA polymerases. Zanotto PM, Gibbs MJ, Gould EA, Holmes EC. J. Virol. 70, 6083-96, (1996). View articlePMID: 8709232

5.Poliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B. Gohara DW, Crotty S, Arnold JJ, Yoder JD, Andino R, Cameron CE. J. Biol. Chem. 275, 25523-32, (2000). View articlePMID: 10827187

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