Uncoupling of protease trans-cleavage and helicase activities in pestivirus ns3
文献类型：期刊论文
| 作者 | Zheng, Fengwei1; Lu, Guoliang2; Li, Ling1; Gong, Peng2; Pan, Zishu1 |
| 刊名 | Journal of virology
 |
| 出版日期 | 2017-11-01 |
| 卷号 | 91期号:21页码:19 |
| 关键词 | Pestivirus Ns3 Protease Helicase Crystal structure |
| ISSN号 | 0022-538X |
| DOI | 10.1128/jvi.01094-17 |
| 通讯作者 | Gong, peng(gongpeng@wh.iov.cn) ; Pan, zishu(zspan@whu.edu.cn) |
| 英文摘要 | The nonstructural protein ns3 from the flaviviridae family is a multifunctional protein that contains an n-terminal protease and a c-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. here we report a full-length crystal structure of the classical swine fever virus (csfv) ns3 in complex with its ns4a protease cofactor segment (pcs) at a 2.35-angstrom resolution. the structure reveals a previously unidentified similar to 2,200-angstrom(2) intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the ns3-ns4a cis-cleavage event. although this conformation is incompatible with protease trans-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo. our work reveals important features of protease-helicase coordination in pestivirus ns3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. importance many rna viruses encode helicases to aid their rna genome replication and transcription by unwinding structured rna. being naturally fused to a protease participating in viral polyprotein processing, the ns3 helicases encoded by the flaviviridae family viruses are unique. therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. here we report a previously unidentified conformation of pestivirus ns3 in complex with its ns4a protease cofactor segment (pcs). this conformational state is related to the protease cis-cleavage event and is optimal for the function of helicase. this work provides an important basis to understand how different enzymatic activities of ns3 may be achieved by the coordination between the protease and helicase through different conformational states. |
| WOS关键词 | HEPATITIS-C VIRUS ; SWINE-FEVER VIRUS ; VIRAL DIARRHEA VIRUS ; WEST-NILE-VIRUS ; NONSTRUCTURAL PROTEIN-3 ; CRYSTAL-STRUCTURE ; DENGUE VIRUS ; SERINE-PROTEASE ; RNA HELICASE ; CATALYTIC DOMAIN |
| WOS研究方向 | Virology |
| WOS类目 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000413195400031 |
| 出版者 | AMER SOC MICROBIOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373400 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Gong, Peng; Pan, Zishu |
| 作者单位 | 1.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan, Hubei, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zheng, Fengwei,Lu, Guoliang,Li, Ling,et al. Uncoupling of protease trans-cleavage and helicase activities in pestivirus ns3[J]. Journal of virology,2017,91(21):19. |
| APA | Zheng, Fengwei,Lu, Guoliang,Li, Ling,Gong, Peng,&Pan, Zishu.(2017).Uncoupling of protease trans-cleavage and helicase activities in pestivirus ns3.Journal of virology,91(21),19. |
| MLA | Zheng, Fengwei,et al."Uncoupling of protease trans-cleavage and helicase activities in pestivirus ns3".Journal of virology 91.21(2017):19. |
入库方式： iSwitch采集
来源：武汉病毒研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。