尼帕病毒聚合酶蛋白多聚化结构域中的一个保守碱性区域和中心环对于聚合酶功能是必需的。
A Conserved Basic Patch and Central Kink in the Nipah Virus Phosphoprotein Multimerization Domain Are Essential for Polymerase Function.
机构信息
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
出版信息
Structure. 2019 Apr 2;27(4):660-668.e4. doi: 10.1016/j.str.2019.01.012. Epub 2019 Feb 21.
Abstract
Nipah virus is a highly lethal zoonotic pathogen found in Southeast Asia that has caused human encephalitis outbreaks with 40%-70% mortality. NiV encodes its own RNA-dependent RNA polymerase within the large protein, L. Efficient polymerase activity requires the phosphoprotein, P, which tethers L to its template, the viral nucleocapsid. P is a multifunctional protein with modular domains. The central P multimerization domain is composed of a long, tetrameric coiled coil. We investigated the importance of structural features found in this domain for polymerase function using a newly constructed NiV bicistronic minigenome assay. We identified a conserved basic patch and central kink in the coiled coil that are important for polymerase function, with R555 being absolutely essential. This basic patch and central kink are conserved in the related human pathogens measles and mumps viruses, suggesting that this mechanism may be conserved.
摘要
寨卡病毒是一种高度致命的人畜共患病原体，存在于东南亚地区，已导致人类脑炎爆发，死亡率为 40%-70%。NiV 在其大蛋白 L 内编码其自身的 RNA 依赖性 RNA 聚合酶。有效的聚合酶活性需要磷蛋白 P，它将 L 连接到其模板（病毒核衣壳）上。P 是一种具有模块化结构域的多功能蛋白。中央 P 多聚化结构域由一个长的四聚体卷曲螺旋组成。我们使用新构建的 NiV 双顺反子小基因组测定法研究了该结构域中发现的结构特征对聚合酶功能的重要性。我们鉴定了卷曲螺旋中对聚合酶功能很重要的保守碱性斑和中央拐点，其中 R555 是绝对必需的。该碱性斑和中央拐点在相关的人类病原体麻疹和腮腺炎病毒中保守存在，这表明该机制可能是保守的。
相似文献
1
A Conserved Basic Patch and Central Kink in the Nipah Virus Phosphoprotein Multimerization Domain Are Essential for Polymerase Function.尼帕病毒聚合酶蛋白多聚化结构域中的一个保守碱性区域和中心环对于聚合酶功能是必需的。
Structure. 2019 Apr 2;27(4):660-668.e4. doi: 10.1016/j.str.2019.01.012. Epub 2019 Feb 21.
2
Biochemical and structural studies of the oligomerization domain of the Nipah virus phosphoprotein: evidence for an elongated coiled-coil homotrimer.尼帕病毒磷酸蛋白寡聚结构域的生化和结构研究：长型卷曲螺旋同三聚体的证据。
Virology. 2013 Nov;446(1-2):162-72. doi: 10.1016/j.virol.2013.07.031. Epub 2013 Aug 28.
3
Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase.副黏病毒聚合酶介导的 RNA 合成的起始、延伸和终止。
PLoS Pathog. 2018 Feb 9;14(2):e1006889. doi: 10.1371/journal.ppat.1006889. eCollection 2018 Feb.
4
Structure of the nucleocapsid-binding domain from the mumps virus polymerase; an example of protein folding induced by crystallization.腮腺炎病毒聚合酶核衣壳结合结构域的结构；晶体诱导蛋白质折叠的一个实例。
J Mol Biol. 2008 Jun 13;379(4):719-31. doi: 10.1016/j.jmb.2007.12.080. Epub 2008 Jan 11.
5
Bipartite interface of the measles virus phosphoprotein X domain with the large polymerase protein regulates viral polymerase dynamics.麻疹病毒磷蛋白 X 结构域与大聚合酶蛋白的二分界面调节病毒聚合酶动力学。
PLoS Pathog. 2019 Aug 5;15(8):e1007995. doi: 10.1371/journal.ppat.1007995. eCollection 2019 Aug.
6
Indiscriminate activities of different henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems.不同亨尼帕病毒聚合酶复合蛋白的随意活动使得在杂交系统中能高效进行微型基因组复制。
J Virol. 2024 Jun 13;98(6):e0050324. doi: 10.1128/jvi.00503-24. Epub 2024 May 23.
7
'Drc', a structurally novel ssDNA-binding transcription regulator of N4-related bacterial viruses.'Drc'，一种与 N4 相关的细菌病毒的结构新颖的 ssDNA 结合转录调控因子。
Nucleic Acids Res. 2020 Jan 10;48(1):445-459. doi: 10.1093/nar/gkz1048.
8
The phosphoprotein (P) and L binding sites reside in the N-terminus of the L subunit of the measles virus RNA polymerase.磷蛋白（P）和L的结合位点位于麻疹病毒RNA聚合酶L亚基的N端。
Virology. 2004 Oct 1;327(2):297-306. doi: 10.1016/j.virol.2004.07.002.
9
Structure of the Nipah virus polymerase phosphoprotein complex.尼帕病毒聚合酶磷蛋白复合物的结构。
Nat Commun. 2024 Oct 7;15(1):8673. doi: 10.1038/s41467-024-52701-y.
10
Plasticity in structural and functional interactions between the phosphoprotein and nucleoprotein of measles virus.麻疹病毒磷蛋白和核蛋白之间结构和功能相互作用的可塑性。
J Biol Chem. 2012 Apr 6;287(15):11951-67. doi: 10.1074/jbc.M111.333088. Epub 2012 Feb 8.
引用本文的文献
1
Construction of Minigenome Replicon of Nipah Virus and Investigation of Biological Activity.尼帕病毒微型基因组复制子的构建及生物学活性研究
Viruses. 2025 May 15;17(5):707. doi: 10.3390/v17050707.
2
Cryo-EM structures of Nipah virus polymerase complex reveal highly varied interactions between L and P proteins among paramyxoviruses.尼帕病毒聚合酶复合物的冷冻电镜结构揭示了副粘病毒中L蛋白和P蛋白之间高度多样的相互作用。
Protein Cell. 2025 Feb 18. doi: 10.1093/procel/pwaf014.
3
Structure of the Nipah virus polymerase complex.尼帕病毒聚合酶复合体的结构。
EMBO J. 2025 Jan;44(2):563-586. doi: 10.1038/s44318-024-00321-z. Epub 2024 Dec 30.
4
Henipaviruses: epidemiology, ecology, disease, and the development of vaccines and therapeutics.亨尼帕病毒：流行病学、生态学、疾病以及疫苗和治疗方法的发展
Clin Microbiol Rev. 2025 Mar 13;38(1):e0012823. doi: 10.1128/cmr.00128-23. Epub 2024 Dec 23.
5
Structure of the Nipah virus polymerase phosphoprotein complex.尼帕病毒聚合酶磷蛋白复合物的结构。
Nat Commun. 2024 Oct 7;15(1):8673. doi: 10.1038/s41467-024-52701-y.
6
A Comparative Assessment of the Pathogenic Potential of Newly Discovered Henipaviruses.新发现的亨尼帕病毒致病潜力的比较评估
Pathogens. 2024 Jul 16;13(7):587. doi: 10.3390/pathogens13070587.
7
Indiscriminate activities of different henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems.不同亨尼帕病毒聚合酶复合蛋白的随意活动使得在杂交系统中能高效进行微型基因组复制。
J Virol. 2024 Jun 13;98(6):e0050324. doi: 10.1128/jvi.00503-24. Epub 2024 May 23.
8
Structures of the mumps virus polymerase complex via cryo-electron microscopy.通过冷冻电镜技术观察腮腺炎病毒聚合酶复合物的结构。
Nat Commun. 2024 May 17;15(1):4189. doi: 10.1038/s41467-024-48389-9.
9
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination.单次剂量黏膜复制子-颗粒疫苗可预防尼帕病毒感染，在接种后 3 天内可有效抵抗致死性感染。
Sci Adv. 2023 Aug 4;9(31):eadh4057. doi: 10.1126/sciadv.adh4057.
10
Genomic characterization, transcriptome analysis, and pathogenicity of the Nipah virus (Indian isolate).尼帕病毒（印度分离株）的基因组特征、转录组分析和致病性。
Virulence. 2023 Dec;14(1):2224642. doi: 10.1080/21505594.2023.2224642.
本文引用的文献
1
Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase.副黏病毒聚合酶介导的 RNA 合成的起始、延伸和终止。
PLoS Pathog. 2018 Feb 9;14(2):e1006889. doi: 10.1371/journal.ppat.1006889. eCollection 2018 Feb.
2
Oligomerization of Mumps Virus Phosphoprotein.腮腺炎病毒磷蛋白的寡聚化
J Virol. 2015 Nov;89(21):11002-10. doi: 10.1128/JVI.01719-15. Epub 2015 Aug 26.
3
The paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics.作为下一代抗副粘病毒疗法靶点的副粘病毒聚合酶复合体
Front Microbiol. 2015 May 12;6:459. doi: 10.3389/fmicb.2015.00459. eCollection 2015.
4
Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone.尼帕病毒未组装核蛋白与其病毒伴侣复合物的结构。
Nat Struct Mol Biol. 2014 Sep;21(9):754-9. doi: 10.1038/nsmb.2868. Epub 2014 Aug 10.
5
Crystal structure of the nipah virus phosphoprotein tetramerization domain.尼帕病毒磷蛋白四聚化结构域的晶体结构
J Virol. 2014 Jan;88(1):758-62. doi: 10.1128/JVI.02294-13. Epub 2013 Oct 23.
6
How good are my data and what is the resolution?我的数据质量如何，分辨率是多少？
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14. doi: 10.1107/S0907444913000061. Epub 2013 Jun 13.
7
Structural and functional characterization of the mumps virus phosphoprotein.副黏病毒磷酸蛋白的结构与功能特征分析。
J Virol. 2013 Jul;87(13):7558-68. doi: 10.1128/JVI.00653-13. Epub 2013 May 1.
8
Structure of the tetramerization domain of measles virus phosphoprotein.麻疹病毒磷蛋白四聚化结构域。
J Virol. 2013 Jun;87(12):7166-9. doi: 10.1128/JVI.00487-13. Epub 2013 Apr 10.
9
The mFruit collection of monomeric fluorescent proteins.单体荧光蛋白的mFruit系列
Clin Chem. 2013 Feb;59(2):440-1. doi: 10.1373/clinchem.2012.194837. Epub 2012 Dec 4.
10
Distinct and overlapping roles of Nipah virus P gene products in modulating the human endothelial cell antiviral response.在调节人类内皮细胞抗病毒反应方面，寨卡病毒 P 基因产物具有独特和重叠的作用。
PLoS One. 2012;7(10):e47790. doi: 10.1371/journal.pone.0047790. Epub 2012 Oct 19.
Zotero 插件