• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

单股负链RNA病毒L蛋白必需结构域的X射线晶体结构及活性

X-ray structure and activities of an essential Mononegavirales L-protein domain.

作者信息

Paesen Guido C, Collet Axelle, Sallamand Corinne, Debart Françoise, Vasseur Jean-Jacques, Canard Bruno, Decroly Etienne, Grimes Jonathan M

机构信息

Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.

AFMB, CNRS, Aix-Marseille University, UMR 7257, Case 925, 163 Avenue de Luminy, 13288 Marseille, France.

出版信息

Nat Commun. 2015 Nov 9;6:8749. doi: 10.1038/ncomms9749.

DOI:10.1038/ncomms9749
PMID:26549102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4659945/
Abstract

The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2'O and N7 positions, and also displays nucleotide triphosphatase activity.

摘要

单股负链RNA病毒的L蛋白具备基因组复制和转录的所有催化活性。它包含六个保守结构域（CR-I至-VI；图1a）。CR-III与聚合酶和聚腺苷酸化活性相关，CR-V与mRNA加帽相关，CR-VI与帽甲基化相关。然而，这些活性是如何协同运作的却知之甚少。在此，我们展示了人偏肺病毒L蛋白一部分（即由CR-VI及其C端保守性较差的区域（即+结构域）组成的CR-VI+）的2.2埃X射线结构及活性。CR-VI结构域具有甲基转移酶折叠结构，除了典型的S-腺苷甲硫氨酸结合位点（(SAM)P）外，还包含一个可容纳核苷的新口袋（(NS)P）。CR-VI缺乏明显的帽结合位点，并且由于突出的+结构域，容纳正在进行甲基化的核苷酸的(SAM)P邻接位点（(SUB)P）异常狭窄。CR-VI+依次对帽的2'O和N7位置进行甲基化，并且还表现出核苷酸三磷酸酶活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/0e24ae640bf2/41467_2015_Article_BFncomms9749_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/6075d9ec21bd/41467_2015_Article_BFncomms9749_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/1b76d030fdc4/41467_2015_Article_BFncomms9749_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/042db24e29fb/41467_2015_Article_BFncomms9749_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/43ba1329c8b9/41467_2015_Article_BFncomms9749_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/3fcda83b59e7/41467_2015_Article_BFncomms9749_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/ee06cebb1a4c/41467_2015_Article_BFncomms9749_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/0e24ae640bf2/41467_2015_Article_BFncomms9749_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/6075d9ec21bd/41467_2015_Article_BFncomms9749_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/1b76d030fdc4/41467_2015_Article_BFncomms9749_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/042db24e29fb/41467_2015_Article_BFncomms9749_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/43ba1329c8b9/41467_2015_Article_BFncomms9749_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/3fcda83b59e7/41467_2015_Article_BFncomms9749_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/ee06cebb1a4c/41467_2015_Article_BFncomms9749_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dae/7091620/0e24ae640bf2/41467_2015_Article_BFncomms9749_Fig7_HTML.jpg

相似文献

1
X-ray structure and activities of an essential Mononegavirales L-protein domain.单股负链RNA病毒L蛋白必需结构域的X射线晶体结构及活性
Nat Commun. 2015 Nov 9;6:8749. doi: 10.1038/ncomms9749.
2
Sequence-function analysis of the Sendai virus L protein domain VI.对仙台病毒 L 蛋白结构域 VI 的序列-功能分析。
Virology. 2010 Sep 30;405(2):370-82. doi: 10.1016/j.virol.2010.06.019. Epub 2010 Jul 6.
3
Recognition of RNA cap in the Wesselsbron virus NS5 methyltransferase domain: implications for RNA-capping mechanisms in Flavivirus.西塞尔布伦病毒NS5甲基转移酶结构域中RNA帽的识别：对黄病毒RNA加帽机制的启示
J Mol Biol. 2009 Jan 9;385(1):140-52. doi: 10.1016/j.jmb.2008.10.028. Epub 2008 Oct 19.
4
Amino acid residues within conserved domain VI of the vesicular stomatitis virus large polymerase protein essential for mRNA cap methyltransferase activity.水泡性口炎病毒大聚合酶蛋白保守结构域VI内的氨基酸残基对mRNA帽甲基转移酶活性至关重要。
J Virol. 2005 Nov;79(21):13373-84. doi: 10.1128/JVI.79.21.13373-13384.2005.
5
Identification of sendai virus L protein amino acid residues affecting viral mRNA cap methylation.鉴定影响病毒mRNA帽甲基化的仙台病毒L蛋白氨基酸残基。
J Virol. 2009 Feb;83(4):1669-81. doi: 10.1128/JVI.01438-08. Epub 2008 Dec 3.
6
The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure.苏丹埃博拉病毒 L 蛋白的甲基转移酶结构域特异性地靶向 RNA 底物的内部腺苷，除了帽结构。
Nucleic Acids Res. 2018 Sep 6;46(15):7902-7912. doi: 10.1093/nar/gky637.
7
Biochemical characterization of the (nucleoside-2'O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n).使用纯化的加帽 RNA 寡核苷酸 (7Me)GpppAC(n) 和 GpppAC(n) 对登革热病毒蛋白 NS5 的（核苷-2'O）-甲基转移酶活性进行生化特性分析。
J Gen Virol. 2010 Jan;91(Pt 1):112-21. doi: 10.1099/vir.0.015511-0. Epub 2009 Sep 23.
8
Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5.登革病毒NS5甲基转移酶结构域对短帽状RNA甲基化及5'-RNA序列要求的结构与功能分析
J Mol Biol. 2007 Sep 21;372(3):723-36. doi: 10.1016/j.jmb.2007.07.005. Epub 2007 Jul 12.
9
Analysis of a structural homology model of the 2'-O-ribose methyltransferase domain within the vesicular stomatitis virus L protein.水疱性口炎病毒L蛋白中2'-O-核糖甲基转移酶结构域的结构同源性模型分析。
Virology. 2008 Dec 5;382(1):69-82. doi: 10.1016/j.virol.2008.08.041. Epub 2008 Oct 11.
10
West Nile virus methyltransferase catalyzes two methylations of the viral RNA cap through a substrate-repositioning mechanism.西尼罗河病毒甲基转移酶通过底物重定位机制催化病毒RNA帽的两次甲基化。
J Virol. 2008 May;82(9):4295-307. doi: 10.1128/JVI.02202-07. Epub 2008 Feb 27.

引用本文的文献

1
Structure and stabilization of the antigenic glycoprotein building blocks of the New World mammarenavirus spike complex.新大陆沙粒病毒刺突复合体抗原糖蛋白结构单元的结构与稳定性
mBio. 2025 Jul 9;16(7):e0107625. doi: 10.1128/mbio.01076-25. Epub 2025 Jun 13.
2
Structure of the measles virus ternary polymerase complex.麻疹病毒三元聚合酶复合体的结构
Nat Commun. 2025 Apr 23;16(1):3819. doi: 10.1038/s41467-025-58985-y.
3
Structural basis of Nipah virus RNA synthesis.尼帕病毒RNA合成的结构基础。

本文引用的文献

1
Crystal structure of the RNA-dependent RNA polymerase from influenza C virus.丙型流感病毒RNA依赖的RNA聚合酶的晶体结构
Nature. 2015 Nov 5;527(7576):114-7. doi: 10.1038/nature15525. Epub 2015 Oct 26.
2
Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy.基于电子冷冻显微镜技术的水疱性口炎病毒L蛋白结构
Cell. 2015 Jul 16;162(2):314-327. doi: 10.1016/j.cell.2015.06.018. Epub 2015 Jul 2.
3
Structural insight into cap-snatching and RNA synthesis by influenza polymerase.流感聚合酶的帽抢夺和 RNA 合成的结构见解。
Nat Commun. 2025 Mar 6;16(1):2261. doi: 10.1038/s41467-025-57219-5.
4
Cryo-EM structure of Nipah virus L-P polymerase complex.尼帕病毒L-P聚合酶复合物的冷冻电镜结构
Nat Commun. 2024 Dec 3;15(1):10524. doi: 10.1038/s41467-024-54994-5.
5
How does the polymerase of non-segmented negative strand RNA viruses commit to transcription or genome replication?非节段负链 RNA 病毒的聚合酶如何进行转录或基因组复制？
J Virol. 2024 Aug 20;98(8):e0033224. doi: 10.1128/jvi.00332-24. Epub 2024 Jul 30.
6
The complete pathway for co-transcriptional mRNA maturation within a large protein of a non-segmented negative-strand RNA virus.非节段负链 RNA 病毒中一个大蛋白内共转录 mRNA 成熟的完整途径。
Nucleic Acids Res. 2024 Sep 9;52(16):9803-9820. doi: 10.1093/nar/gkae659.
7
Conserved allosteric inhibitory site on the respiratory syncytial virus and human metapneumovirus RNA-dependent RNA polymerases.呼吸道合胞病毒和人偏肺病毒 RNA 依赖性 RNA 聚合酶上的保守变构抑制位点。
Commun Biol. 2023 Jun 19;6(1):649. doi: 10.1038/s42003-023-04990-0.
8
Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities.呼吸道合胞病毒 L 蛋白嵌入 RNA 聚合酶和加帽活性的生物化学。
Viruses. 2023 Jan 25;15(2):341. doi: 10.3390/v15020341.
9
Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect.HIV-1 基因组中的内部 RNA 2'O-甲基化可抵抗 ISG20 核酸酶介导的抗病毒作用。
Nucleic Acids Res. 2023 Apr 11;51(6):2501-2515. doi: 10.1093/nar/gkac996.
10
Methyltransferases of .. 的甲基转移酶
Biomolecules. 2022 Sep 6;12(9):1247. doi: 10.3390/biom12091247.
Nature. 2014 Dec 18;516(7531):361-6. doi: 10.1038/nature14009. Epub 2014 Nov 19.
4
Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation.参与mRNA帽结构形成的人类2'-O-核糖甲基转移酶的结构分析。
Nat Commun. 2014;5:3004. doi: 10.1038/ncomms4004.
5
Advances in Rosetta structure prediction for difficult molecular-replacement problems.针对困难分子置换问题的罗塞塔结构预测进展。
Acta Crystallogr D Biol Crystallogr. 2013 Nov;69(Pt 11):2202-8. doi: 10.1107/S0907444913023305. Epub 2013 Oct 12.
6
Decision making in xia2.xia2中的决策制定
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1260-73. doi: 10.1107/S0907444913015308. Epub 2013 Jun 18.
7
Development of specific dengue virus 2'-O- and N7-methyltransferase assays for antiviral drug screening.建立用于抗病毒药物筛选的特定登革病毒 2'-O- 和 N7-甲基转移酶测定法。
Antiviral Res. 2013 Sep;99(3):292-300. doi: 10.1016/j.antiviral.2013.06.001. Epub 2013 Jun 12.
8
Synthesis of 5' cap-0 and cap-1 RNAs using solid-phase chemistry coupled with enzymatic methylation by human (guanine-N⁷)-methyl transferase.使用固相化学结合人（鸟嘌呤-N7）-甲基转移酶的酶促甲基化合成 5' 帽-0 和帽-1 RNA。
RNA. 2012 Apr;18(4):856-68. doi: 10.1261/rna.030932.111. Epub 2012 Feb 14.
9
Conventional and unconventional mechanisms for capping viral mRNA.帽状结构形成病毒 mRNA 的传统和非传统机制。
Nat Rev Microbiol. 2011 Dec 5;10(1):51-65. doi: 10.1038/nrmicro2675.
10
Ten years of human metapneumovirus research.人类偏肺病毒研究十年。
J Clin Virol. 2012 Feb;53(2):97-105. doi: 10.1016/j.jcv.2011.10.002. Epub 2011 Nov 9.