Cryo-EM Structure of Influenza Virus RNA Polymerase Complex at 4.3 Å Resolution

被引：74

作者：

Chang, Shenghai ^{[1
]}

Sun, Dapeng ^{[1
]}

Liang, Huanhuan ^{[1
]}

Wang, Jia ^{[2
]}

Li, Jun ^{[1
]}

Guo, Lu ^{[1
]}

Wang, Xiangli ^{[1
]}

Guan, Chengcheng ^{[1
]}

Boruah, Bhargavi M. ^{[1
]}

Yuan, Lingmin ^{[1
]}

Feng, Feng ^{[1
]}

Yang, Mingrui ^{[1
]}

Wang, Lulan ^{[5
,6
,7
]}

Wang, Yao ^{[5
,6
,7
]}

Wojdyla, Justyna ^{[3
]}

Li, Lanjuan ^{[4
]}

Wang, Jiawei ^{[2
]}

Wang, Meitian ^{[3
]}

Cheng, Genhong ^{[5
,6
,7
]}

Wang, Hong-Wei ^{[2
]}

Liu, Yingfang ^{[1
,4
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, Inst Biophys, Natl Key Lab Biomacromol, Beijing 100101, Peoples R China

[2] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Minist Educ,Key Lab Prot Sci,Ctr Struct Biol, Beijing 100084, Peoples R China

[3] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland

[4] Zhejiang Univ, Affiliated Hosp 1, State Key Lab DTID, Coll Med,Collaborat Innovat Ctr DTID, Hangzhou 310003, Zhejiang, Peoples R China

[5] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[6] Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Syst Med, Beijing 100005, Peoples R China

[7] Peking Union Med Coll, Beijing 100005, Peoples R China

来源：

MOLECULAR CELL | 2015年 / 57卷 / 05期

关键词：

CRYSTAL-STRUCTURE; A VIRUS; PB2; SUBUNIT; CAP-BINDING; ENDONUCLEASE; REVEALS; PA; REPLICATION; MECHANISMS; INITIATION;

D O I：

10.1016/j.molcel.2014.12.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Replication and transcription of influenza virus genome mainly depend on its RNA-dependent RNA polymerase (RdRP), composed of the PA, PB1, and PB2 subunits. Although extensively studied, the underlying mechanism of the RdRP complex is still unclear. Here we report the biochemical characterization of influenza RdRP subcomplex comprising PA, PB1, and N terminus of PB2, which exist as dimer in solution and can assemble into a tetramer state, regulated by vRNA promoter. Using single-particle cryo-electron microscopy, we have reconstructed the RdRP tetramer complex at 4.3 angstrom, highlighting the assembly and interfaces between monomers within the tetrameric structure. The individual RdRP subcomplex contains all the characterized motifs and appears as a cage-like structure. High-throughput mutagenesis profiling revealed that residues involved in the oligomer state formation are critical for viral life cycle. Our results lay a solid base for understanding the mechanism of replication of influenza and other negative-stranded RNA viruses.

引用

页码：925 / 935

页数：11

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