丙型肝炎病毒RNA依赖性RNA聚合酶膜插入序列是一个跨膜区段。
The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment.
作者信息
Ivashkina Natalia, Wölk Benno, Lohmann Volker, Bartenschlager Ralf, Blum Hubert E, Penin François, Moradpour Darius
机构信息
Department of Medicine II, University Hospital, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
出版信息
J Virol. 2002 Dec;76(24):13088-93. doi: 10.1128/jvi.76.24.13088-13093.2002.
Abstract
The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) belongs to a class of membrane proteins termed tail-anchored proteins. Here, we show that the HCV RdRp C-terminal membrane insertion sequence traverses the phospholipid bilayer as a transmembrane segment. Moreover, the HCV RdRp was found to be retained in the endoplasmic reticulum (ER) or an ER-derived modified compartment both following transient transfection and in the context of a subgenomic replicon. An absolutely conserved GVG motif was not essential for membrane insertion but possibly provides a docking site for transmembrane protein-protein interactions. These findings have important implications for the functional architecture of the HCV replication complex.
摘要
丙型肝炎病毒（HCV）的RNA依赖性RNA聚合酶（RdRp）属于一类被称为尾锚定蛋白的膜蛋白。在此，我们表明HCV RdRp的C末端膜插入序列作为跨膜片段穿过磷脂双层。此外，无论是在瞬时转染后还是在亚基因组复制子的背景下，都发现HCV RdRp保留在内质网（ER）或源自ER的修饰区室中。一个绝对保守的GVG基序对膜插入并非必不可少，但可能为跨膜蛋白-蛋白相互作用提供一个对接位点。这些发现对HCV复制复合体的功能结构具有重要意义。
相似文献
1
The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment.丙型肝炎病毒RNA依赖性RNA聚合酶膜插入序列是一个跨膜区段。
J Virol. 2002 Dec;76(24):13088-93. doi: 10.1128/jvi.76.24.13088-13093.2002.
2
The C-terminal transmembrane domain of hepatitis C virus (HCV) RNA polymerase is essential for HCV replication in vivo.丙型肝炎病毒（HCV）RNA聚合酶的C末端跨膜结构域对于HCV在体内的复制至关重要。
J Virol. 2004 Apr;78(7):3797-802. doi: 10.1128/jvi.78.7.3797-3802.2004.
3
Membrane association of the RNA-dependent RNA polymerase is essential for hepatitis C virus RNA replication.RNA依赖性RNA聚合酶的膜结合对于丙型肝炎病毒RNA复制至关重要。
J Virol. 2004 Dec;78(23):13278-84. doi: 10.1128/JVI.78.23.13278-13284.2004.
4
Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase.丙型肝炎病毒RNA依赖性RNA聚合酶膜结合的决定因素。
J Biol Chem. 2001 Nov 23;276(47):44052-63. doi: 10.1074/jbc.M103358200.
5
Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase.丙型肝炎病毒 RNA 的复制需要 NS5B RNA 依赖性 RNA 聚合酶跨膜结构域内的保守结构基序。
J Virol. 2010 Nov;84(21):11580-4. doi: 10.1128/JVI.01519-10. Epub 2010 Aug 25.
6
Mutations in NS5B polymerase of hepatitis C virus: impacts on in vitro enzymatic activity and viral RNA replication in the subgenomic replicon cell culture.丙型肝炎病毒NS5B聚合酶的突变：对亚基因组复制子细胞培养中体外酶活性和病毒RNA复制的影响。
Virology. 2002 Jun 5;297(2):298-306. doi: 10.1006/viro.2002.1461.
7
Replication of hepatitis C virus RNA occurs in a membrane-bound replication complex containing nonstructural viral proteins and RNA.丙型肝炎病毒RNA的复制发生在一个包含非结构病毒蛋白和RNA的膜结合复制复合物中。
J Gen Virol. 2003 Oct;84(Pt 10):2761-2769. doi: 10.1099/vir.0.19305-0.
8
A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication.丙型肝炎病毒RNA复制需要编码NS5B RNA依赖性RNA聚合酶的序列中的一个顺式作用复制元件。
J Virol. 2004 Feb;78(3):1352-66. doi: 10.1128/jvi.78.3.1352-1366.2004.
9
Interaction between Nonstructural Proteins NS4B and NS5A Is Essential for Proper NS5A Localization and Hepatitis C Virus RNA Replication.非结构蛋白NS4B与NS5A之间的相互作用对于NS5A的正确定位和丙型肝炎病毒RNA复制至关重要。
J Virol. 2016 Jul 27;90(16):7205-7218. doi: 10.1128/JVI.00037-16. Print 2016 Aug 15.
10
Evidence for Internal Initiation of RNA Synthesis by the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5B .丙型肝炎病毒 RNA 依赖的 RNA 聚合酶 NS5B 内部引发 RNA 合成的证据。
J Virol. 2019 Sep 12;93(19). doi: 10.1128/JVI.00525-19. Print 2019 Oct 1.
引用本文的文献
1
A Multi-Model Machine Learning Framework for Identifying Raloxifene as a Novel RNA Polymerase Inhibitor from FDA-Approved Drugs.一种用于从FDA批准的药物中鉴定雷洛昔芬作为新型RNA聚合酶抑制剂的多模型机器学习框架。
Curr Issues Mol Biol. 2025 Apr 28;47(5):315. doi: 10.3390/cimb47050315.
2
ATAD1 inhibits hepatitis C virus infection by removing the viral TA-protein NS5B from mitochondria.ATAD1 通过将病毒 TA 蛋白 NS5B 从线粒体中移除来抑制丙型肝炎病毒感染。
EMBO Rep. 2023 Nov 6;24(11):e56614. doi: 10.15252/embr.202256614. Epub 2023 Oct 3.
3
Nanosized Particles Assembled by a Recombinant Virus Protein Are Able to Encapsulate Negatively Charged Molecules and Structured RNA.由重组病毒蛋白组装而成的纳米颗粒能够包裹带负电荷的分子和结构化RNA。
Polymers (Basel). 2021 Mar 11;13(6):858. doi: 10.3390/polym13060858.
4
Changes of Gut-Microbiota-Liver Axis in Hepatitis C Virus Infection.丙型肝炎病毒感染中肠道微生物群-肝脏轴的变化
Biology (Basel). 2021 Jan 13;10(1):55. doi: 10.3390/biology10010055.
5
Human guanylate binding proteins: nanomachines orchestrating host defense.人类鸟苷酸结合蛋白：调控宿主防御的纳米机器。
FEBS J. 2021 Oct;288(20):5826-5849. doi: 10.1111/febs.15662. Epub 2021 Jan 12.
6
Developments in the HCV Screening Technologies Based on the Detection of Antigens and Antibodies.基于抗原和抗体检测的 HCV 筛查技术的发展。
Sensors (Basel). 2019 Sep 30;19(19):4257. doi: 10.3390/s19194257.
7
Genotyping & diagnostic methods for hepatitis C virus: A need of low-resource countries.丙型肝炎病毒基因分型和诊断方法：资源匮乏国家的需求。
Indian J Med Res. 2018 May;147(5):445-455. doi: 10.4103/ijmr.IJMR_1850_16.
8
NMR reveals the intrinsically disordered domain 2 of NS5A protein as an allosteric regulator of the hepatitis C virus RNA polymerase NS5B.核磁共振揭示了NS5A蛋白的内在无序结构域2作为丙型肝炎病毒RNA聚合酶NS5B的变构调节剂。
J Biol Chem. 2017 Nov 3;292(44):18024-18043. doi: 10.1074/jbc.M117.813766. Epub 2017 Sep 14.
9
Discovery of Novel Allosteric HCV NS5B Inhibitors. 2. Lactam-Containing Thiophene Carboxylates.新型变构丙型肝炎病毒NS5B抑制剂的发现。2. 含内酰胺的噻吩羧酸盐。
ACS Med Chem Lett. 2017 Jan 31;8(2):251-255. doi: 10.1021/acsmedchemlett.6b00479. eCollection 2017 Feb 9.
10
The role of HCV proteins on treatment outcomes.丙型肝炎病毒（HCV）蛋白对治疗结果的作用。
Virol J. 2015 Dec 15;12:217. doi: 10.1186/s12985-015-0450-x.
本文引用的文献
1
A class of membrane proteins with a C-terminal anchor.一类具有C末端锚定结构的膜蛋白。
Trends Cell Biol. 1993 Mar;3(3):72-5. doi: 10.1016/0962-8924(93)90066-a.
2
Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins.丙型肝炎病毒包膜糖蛋白跨膜结构域的拓扑变化
EMBO J. 2002 Jun 17;21(12):2893-902. doi: 10.1093/emboj/cdf295.
3
Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex.丙型肝炎病毒蛋白的表达会引发不同的膜改变，包括一种候选病毒复制复合体。
J Virol. 2002 Jun;76(12):5974-84. doi: 10.1128/jvi.76.12.5974-5984.2002.
4
Sequences in the 5' nontranslated region of hepatitis C virus required for RNA replication.丙型肝炎病毒RNA复制所需的5'非翻译区序列。
J Virol. 2001 Dec;75(24):12047-57. doi: 10.1128/JVI.75.24.12047-12057.2001.
5
Functional properties of a monoclonal antibody inhibiting the hepatitis C virus RNA-dependent RNA polymerase.一种抑制丙型肝炎病毒RNA依赖性RNA聚合酶的单克隆抗体的功能特性
J Biol Chem. 2002 Jan 4;277(1):593-601. doi: 10.1074/jbc.M108748200. Epub 2001 Oct 18.
6
Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase.丙型肝炎病毒RNA依赖性RNA聚合酶膜结合的决定因素。
J Biol Chem. 2001 Nov 23;276(47):44052-63. doi: 10.1074/jbc.M103358200.
7
Enhancement of hepatitis C virus RNA replication by cell culture-adaptive mutations.细胞培养适应性突变增强丙型肝炎病毒RNA复制
J Virol. 2001 May;75(10):4614-24. doi: 10.1128/JVI.75.10.4614-4624.2001.
8
Intracellular functions of N-linked glycans.N-连接聚糖的细胞内功能。
Science. 2001 Mar 23;291(5512):2364-9. doi: 10.1126/science.291.5512.2364.
9
Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes.C末端（尾部）锚定蛋白的靶向作用：了解细胞质活动如何锚定到细胞内膜上。
Traffic. 2001 Jan;2(1):66-71. doi: 10.1034/j.1600-0854.2001.20108.x.
10
Determination of the binding sites of the proton transfer inhibitors Cd2+ and Zn2+ in bacterial reaction centers.细菌反应中心中质子转移抑制剂Cd2+和Zn2+结合位点的测定。
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1542-7. doi: 10.1073/pnas.97.4.1542.
Zotero 插件