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

作　　者：Xiang Fang Guoliang Lu Yanchun Deng Sa Yang Chunsheng Hou Peng Gong 

机构地区：[1]Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430207,China [2]Institute of Bast Fiber Crops,Chinese Academy of Agricultural Sciences,Changsha,410205,China [3]University of Chinese Academy of Sciences,Beijing,100049,China [4]Institute of Apicultural Research,Chinese Academy of Agricultural Sciences,Beijing,100193,China [5]Hubei Jiangxia Laboratory,Wuhan,430207,China

出　　处：《Virologica Sinica》2023年第4期531-540,共10页中国病毒学（英文版）

基　　金：supported by the National Natural Science Foundation of China (31802147 to G.L.,31572471,31811530276 to C.H.);National Key Research and Development Program of China (2018YFA0507200 to P.G.and G.L.);the Agricultural Science and Technology Innovation Program (CAAS-ASTIP-2023-IBFC to C.H.);the Creative Research Group Program of Natural Science Foundation of Hubei Province (2022CFA021 to P.G.);the Central Public-Interest Scientific Institution Basal Research Fund (Y2021YJ25 to C.H.);Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory (JXBS001 to P.G.).

摘　　要：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 3D^(pol).Compared with the Picornaviridae RdRPs such as poliovirus(PV)3D^(pol),the Dicistroviridae representative Israeli acute paralysis virus(IAPV)3D^(pol) has an additional N-terminal extension(NE)region that is about 40-residue 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 3D^(pol),namelyΔ85 andΔ40,both missing the NE region,and the 3D^(pol) protein in these structures exhibited three conformational states.The palm and thumb domains of these IAPV 3D^(pol) structures are largely consistent with those of the PV 3D^(pol) 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 theΔ40 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.

关 键 词：Israeli acute paralysis virus(IAPV) POLIOVIRUS RNA-dependent RNA polymerase(RdRP) Crystal structure Catalytic motif 

分 类 号：S432.41[农业科学—植物病理学]