首页|Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding

Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding

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The Dicistroviridae is a virus family that includes many insect pathogens.These viruses contain a positive-sense RNA genome that is replicated by the virally encoded RNA-dependent RNA polymerase(RdRP)also named 3Dpol.Compared with the Picornaviridae RdRPs such as poliovirus(PV)3Dpol,the Dicistroviridae representative Israeli acute paralysis virus(IAPV)3Dpol has an additional N-terminal extension(NE)region that is about 40-res-idue in length.To date,both the structure and catalytic mechanism of the Dicistroviridae RdRP have remain elusive.Here we reported crystal structures of two truncated forms of IAPV 3Dpol,namely Δ85 and Δ40,both missing the NE region,and the 3Dpol protein in these structures exhibited three conformational states.The palm and thumb domains of these IAPV 3Dpol structures are largely consistent with those of the PV 3Dpol structures.However,in all structures,the RdRP fingers domain is partially disordered,while different conformations of RdRP substructures and interactions between them are also present.In particular,a large-scale conformational change occurred in the motif B-middle finger region in one protein chain of the Δ40 structure,while a previously documented alternative conformation of motif A was observed in all IAPV structures.These experimental data on one hand show intrinsic conformational variances of RdRP substructures,and on the other hand suggest possible contribution of the NE region in proper RdRP folding in IAPV.

Israeli acute paralysis virus(IAPV)PoliovirusRNA-dependent RNA polymerase(RdRP)Crystal structureCatalytic motif

Xiang Fang、Guoliang Lu、Yanchun Deng、Sa Yang、Chunsheng Hou、Peng Gong

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Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430207,China

University of Chinese Academy of Sciences,Beijing,100049,China

Institute of Bast Fiber Crops,Chinese Academy of Agricultural Sciences,Changsha,410205,China

Institute of Apicultural Research,Chinese Academy of Agricultural Sciences,Beijing,100193,China

Hubei Jiangxia Laboratory,Wuhan,430207,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaAgricultural Science and Technology Innovation ProgramCreative Research Group Program of Natural Science Foundation of Hubei ProvinceCentral Public-Interest Scientific Institution Basal Research FundKey Biosafety Science and Technology Program of Hubei Jiangxia Laboratory

3180214731572471318115302762018YFA0507200CAAS-ASTIP-2023-IBFC2022CFA021Y2021YJ25JXBS001

2023

10.1016/j.virs.2023.05.002

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(4)
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