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Viruses 2018, 10(2), 59; https://doi.org/10.3390/v10020059

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases

CNRS, Aix-Marseille Université, AFMB, UMR 7257, 163 Avenue de Luminy, 13288 Marseille, France
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Received: 9 January 2018 / Revised: 25 January 2018 / Accepted: 27 January 2018 / Published: 30 January 2018
(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)
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Abstract

Viral RNA-dependent RNA polymerases (RdRps) play a central role not only in viral replication, but also in the genetic evolution of viral RNAs. After binding to an RNA template and selecting 5′-triphosphate ribonucleosides, viral RdRps synthesize an RNA copy according to Watson-Crick base-pairing rules. The copy process sometimes deviates from both the base-pairing rules specified by the template and the natural ribose selectivity and, thus, the process is error-prone due to the intrinsic (in)fidelity of viral RdRps. These enzymes share a number of conserved amino-acid sequence strings, called motifs A–G, which can be defined from a structural and functional point-of-view. A co-relation is gradually emerging between mutations in these motifs and viral genome evolution or observed mutation rates. Here, we review our current knowledge on these motifs and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps. View Full-Text
Keywords: RNA virus; RNA genome; Flavivirus; RNA polymerase; RNA synthesis; nucleotide inhibitor; selectivity; fidelity; active site; mutation RNA virus; RNA genome; Flavivirus; RNA polymerase; RNA synthesis; nucleotide inhibitor; selectivity; fidelity; active site; mutation
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Selisko, B.; Papageorgiou, N.; Ferron, F.; Canard, B. Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases. Viruses 2018, 10, 59.

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