Protein Domain : RNA-directed RNA polymerase, thumb domain, birnavirus IPR046752

Type  Domain
Description  RNA-directed RNA polymerase (RdRp) ( ) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage [ , ]. 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 [ ]. All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organisation has been likened to the shape of a right hand with three subdomains termed fingers, palm and thumb [ ]. Only the catalytic palm subdomain, composed of a four-stranded antiparallel β-sheet with two α-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 synthesised rather than DNA [].The domain organisation [ ] and the 3D structure of the catalytic centre of a wide range of RdPp's, even those with a low overall sequence homology, are conserved. The catalytic centre is formed by several motifs containing a number of conserved amino acid residues.There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage: Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.Mononegavirales (negative-strand RNA viruses with non-segmented genomes).Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.Birnaviridae family of dsRNA viruses.The RNA-directed RNA polymerases in the first of the above superfamilies can be divided into the following three subgroups:All positive-strand RNA eukaryotic viruses with no DNA stage.All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).Reoviridae family of dsRNA viruses.This entry represents the thumb domain of RdRp from Birnavirus, which contain the conserved RdRp motifs that reside in the catalytic "palm"domain ( ) of all classes of polymerases but in a characteristic permuted order, thus, it adopts a unique active site topology [ , ]. Additionally, the birnavirus RdRps lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain of other RdRps [, , ].
Short Name  Birnavirus_RdRp_thumb

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