title: The uncoupling of catalysis and translocation in the viral RNA-dependent RNA polymerase.
abstract: The nucleotide addition cycle of nucleic acid polymerases includes 2 major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. In viral RNA-dependent RNA polymerases (RdRPs), structural and biochemical evidences suggest that these 2 events are not tightly coupled, unlike the situation observed in A-family polymerases such as the bacteriophage T7 RNA polymerase. Recently, an RdRP translocation intermediate crystal structure of enterovirus 71 shed light on how translocation may be controlled by elements within RdRP catalytic motifs, and a series of poliovirus apo RdRP crystal structures explicitly suggest that a motif B loop may assist the movement of the template strand in late stages of transcription. Implications of RdRP catalysis-translocation uncoupling and the remaining challenges to further elucidate RdRP translocation mechanism are also discussed.
authors.affiliation: a Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Xiao Hong Shan, Wuhan , Hubei , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shu
authors.affiliation: a Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Xiao Hong Shan, Wuhan , Hubei , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gong
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D021381:Protein Transport; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D014780:Viruses / Q000737:chemistry / Q000201:enzymology*
chemical_list: D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Active site closure; RNA polymerase; RNA-dependent; crystal structure; nucleotide addition cycle;; translocation