Abstract

RNA dependent RNA polymerase (RdRp) is one of the most versatile enzymes of RNA viruses that is indispensable for replicating the genome as well as for carrying out transcription. The core structural features of RdRps are conserved, despite the divergence in their sequences. The structure of RdRp resembles that of a cupped right hand and consists of fingers, palm and thumb subdomains. The catalysis involves the participation of conserved aspartates and divalent metal ions. Complexes of RdRps with substrates, inhibitors and metal ions provide a comprehensive view of their functional mechanism and offer valuable insights regarding the development of antivirals. In this article, we provide an overview of the structural aspects of RdRps and their complexes from the Group III, IV and V viruses and their structure-based phylogeny.

Highlights

  • RNA genomes dominate the world of viruses

  • The core RNA dependent RNA polymerase (RdRp) domain consists of the thumb, palm and the fingers subdomains that are primarily involved in template binding, polymerization, nucleoside triphosphate (NTP) entry and associated functions (Figure 1A)

  • In the segmented ss (−) RNA viruses, motif G is composed of a helix that interacts with the priming NTPs [56,62,66]

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Summary

Introduction

RNA genomes dominate the world of viruses. Their success results from the possibility of accommodating rapid changes via mutations, which aids in countering constant challenges imposed by the host physiology [1]. RdRps are multi-domain (α and β) proteins belonging to Structural Classification of Proteins (SCOP) class 2.7.7.48. They catalyze RNA-template dependent formation of phosphodiester bonds between ribonucleotides in the presence of divalent metal ions [4]. The host factors include translation factors, protein chaperones, RNA-modifying enzymes, and a few other cellular proteins. These together with the RdRps, constitute the viral replication complexes (VRCs) [3,9]. In many Group IV viruses, VRCs associate with the host membranes to protect the viral RNAs and help segregation of products and templates during replication [12,13].

The Subdomains
The Motifs
The Channels
Additional Structural Elements
Structure-Based Phylogeny of RdRps
Analysis of RdRp Complexes
RdRp Complexes in Reoviridae
RdRp Complexes in Bacteriophages
RdRp Complexes of Caliciviridae
RdRp Complexes of Picornaviridae
RdRp Complexes of Flaviviridae
Conclusions

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