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1

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, No. 44 Xiao Hong Shan, Wuchang District, Wuhan 430071, China

2

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

3

University of Chinese Academy of Sciences, Beijing 100049, China





*

Author to whom correspondence should be addressed.



Academic Editor: Charles A. Collyer

Abstract RNA-dependent RNA polymerases RdRPs from the Flaviviridae family are representatives of viral polymerases that carry out RNA synthesis through a de novo initiation mechanism. They share a ≈ 600-residue polymerase core that displays a canonical viral RdRP architecture resembling an encircled right hand with palm, fingers, and thumb domains surrounding the active site. Polymerase catalytic motifs A–E in the palm and motifs F-G in the fingers are shared by all viral RdRPs with sequence and-or structural conservations regardless of the mechanism of initiation. Different from RdRPs carrying out primer-dependent initiation, Flaviviridae and other de novo RdRPs utilize a priming element often integrated in the thumb domain to facilitate primer-independent initiation. Upon the transition to the elongation phase, this priming element needs to undergo currently unresolved conformational rearrangements to accommodate the growth of the template-product RNA duplex. In the genera of Flavivirus and Pestivirus, the polymerase module in the C-terminal part of the RdRP protein may be regulated in cis by the N-terminal region of the same polypeptide. Either being a methyltransferase in Flavivirus or a functionally unclarified module in Pestivirus, this region could play auxiliary roles for the canonical folding and-or the catalysis of the polymerase, through defined intra-molecular interactions. View Full-Text

Keywords: Flaviviridae; RNA-dependent RNA polymerase; catalytic motif; de novo initiation; elongation; in cis regulation Flaviviridae; RNA-dependent RNA polymerase; catalytic motif; de novo initiation; elongation; in cis regulation





Autor: Jiqin Wu 1,2,3, Weichi Liu 1,2,3 and Peng Gong 1,2,*

Fuente: http://mdpi.com/



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