A unique intra-molecular fidelity-modulating mechanism identified in a viral rna-dependent rna polymerase
文献类型：期刊论文
| 作者 | Liu, Weichi1,2; Shi, Xiaoling1,2; Gong, Peng1 |
| 刊名 | Nucleic acids research
 |
| 出版日期 | 2018-11-16 |
| 卷号 | 46期号:20页码:10840-10854 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gky848 |
| 通讯作者 | Gong, peng(gongpeng@wh.iov.cn) |
| 英文摘要 | Typically not assisted by proofreading, the rna-dependent rna polymerases (rdrps) encoded by the rna viruses may need to independently control its fidelity to fulfill virus viability and fitness. however, the precise mechanism by which the rdrp maintains its optimal fidelity level remains largely elusive. by solving 2.1-2.5 angstrom resolution crystal structures of the classical swine fever virus (csfv) ns5b, an rdrp with a unique naturally fused n-terminal domain (ntd), we identified high-resolution intra-molecular interactions between the ntd and the rdrp palm domain. in order to dissect possible regulatory functions of ntd, we designed mutations at residues y471 and e472 to perturb key interactions at the ntd-rdrp interface. when crystallized, some of these ns5b interface mutants maintained the interface, while the others adopted an 'open' conformation that no longer retained the intra-molecular interactions. data from multiple in vitro rdrp assays indicated that the perturbation of the ntd-rdrp interactions clearly reduced the fidelity level of the rna synthesis, while the processivity of the ns5b elongation complex was not affected. collectively, our work demonstrates an explicit and unique mode of polymerase fidelity modulation and provides a vivid example of co-evolution in multi-domain enzymes. |
| WOS关键词 | STATE KINETIC-ANALYSIS ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; ACTIVE-SITE ; PROOFREADING MECHANISMS ; REVERSE-TRANSCRIPTASE ; LARGE FRAGMENT ; REPLICATION ; INITIATION ; CATALYSIS |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000456709700029 |
| 出版者 | OXFORD UNIV PRESS |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373199 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Gong, Peng |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan 430071, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Weichi,Shi, Xiaoling,Gong, Peng. A unique intra-molecular fidelity-modulating mechanism identified in a viral rna-dependent rna polymerase[J]. Nucleic acids research,2018,46(20):10840-10854. |
| APA | Liu, Weichi,Shi, Xiaoling,&Gong, Peng.(2018).A unique intra-molecular fidelity-modulating mechanism identified in a viral rna-dependent rna polymerase.Nucleic acids research,46(20),10840-10854. |
| MLA | Liu, Weichi,et al."A unique intra-molecular fidelity-modulating mechanism identified in a viral rna-dependent rna polymerase".Nucleic acids research 46.20(2018):10840-10854. |
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来源：武汉病毒研究所
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