炭疽毒素保护性抗原——从预孔到孔的分子开关洞察。
Anthrax toxin protective antigen--insights into molecular switching from prepore to pore.
机构信息
Department of Chemistry, Wichita State University, Wichita, Kansas 67260-0051, USA.
出版信息
Protein Sci. 2012 Jan;21(1):1-12. doi: 10.1002/pro.752.
Abstract
The protective antigen is a key component of the anthrax toxin, as it allows entry of the enzymatic components edema factor and lethal factor into the host cell, through the formation of a membrane spanning pore. This event is absolutely critical for the pathogenesis of anthrax, and although we have yet to understand the mechanism of pore formation, recent developments have provided key insights into how this process may occur. Based on the available data, a model is proposed for the kinetic steps for protective antigen conversion from prepore to pore. In this model, the driving force for pore formation is the formation of the phi (ϕ)-clamp, a region that forms a leak-free seal around the translocating polypeptide. Formation of the ϕ-clamp elicits movements within the prepore that provide steric freedom for the subsequent conformational changes required to form the membrane spanning pore.
摘要
保护性抗原是炭疽毒素的关键组成部分，因为它允许酶成分水肿因子和致死因子通过形成跨膜孔进入宿主细胞。这一事件对炭疽病的发病机制至关重要，尽管我们尚未了解孔形成的机制，但最近的发展为这一过程如何发生提供了关键的见解。基于现有数据，提出了保护性抗原从预孔到孔的转换的动力学步骤模型。在该模型中，孔形成的驱动力是φ（ϕ）-夹的形成，该区域围绕着移位多肽形成无泄漏密封。ϕ-夹的形成引起预孔内的运动，为随后形成跨膜孔所需的构象变化提供空间自由度。
相似文献
1
Anthrax toxin protective antigen--insights into molecular switching from prepore to pore.炭疽毒素保护性抗原——从预孔到孔的分子开关洞察。
Protein Sci. 2012 Jan;21(1):1-12. doi: 10.1002/pro.752.
2
Atomic structure of anthrax protective antigen pore elucidates toxin translocation.炭疽保护性抗原孔的原子结构揭示了毒素转运机制。
Nature. 2015 May 28;521(7553):545-9. doi: 10.1038/nature14247. Epub 2015 Mar 16.
3
Membrane translocation by anthrax toxin.炭疽毒素的膜转位。
Mol Aspects Med. 2009 Dec;30(6):413-22. doi: 10.1016/j.mam.2009.06.003. Epub 2009 Jun 27.
4
Anthrax protective antigen: prepore-to-pore conversion.炭疽保护性抗原：前孔到孔的转变
Biochemistry. 1999 Aug 10;38(32):10432-41. doi: 10.1021/bi990792d.
5
Monitoring anthrax toxin receptor dissociation from the protective antigen by NMR.通过核磁共振监测炭疽毒素受体与保护性抗原的解离
Protein Sci. 2009 Jan;18(1):17-23. doi: 10.1002/pro.26.
6
A receptor-based switch that regulates anthrax toxin pore formation.一种基于受体的开关，调节炭疽毒素孔形成。
PLoS Pathog. 2011 Dec;7(12):e1002354. doi: 10.1371/journal.ppat.1002354. Epub 2011 Dec 8.
7
Probing the pH-dependent prepore to pore transition of Bacillus anthracis protective antigen with differential oxidative protein footprinting.利用差异氧化蛋白质足迹法探究炭疽芽孢杆菌保护性抗原pH依赖性前孔到孔的转变
Biochemistry. 2008 Oct 7;47(40):10694-704. doi: 10.1021/bi800533t. Epub 2008 Sep 12.
8
A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore.苯丙氨酸钳催化蛋白质通过炭疽毒素孔道进行转运。
Science. 2005 Jul 29;309(5735):777-81. doi: 10.1126/science.1113380.
9
A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax Lethal Factor.一种用于研究炭疽致死因子 N 端结构域功能关系的半合成平台。
ACS Chem Biol. 2010 Apr 16;5(4):359-64. doi: 10.1021/cb100003r.
10
Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation.炭疽保护性抗原的苯丙氨酸-427在孔形成和蛋白质转运中均发挥作用。
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4346-51. doi: 10.1073/pnas.0800701105. Epub 2008 Mar 11.
引用本文的文献
1
Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics.塞内卡山谷病毒及其生物标志物TEM8/ANTXR1在癌症治疗中的作用演变
Front Mol Biosci. 2022 Aug 26;9:930207. doi: 10.3389/fmolb.2022.930207. eCollection 2022.
2
Impact of Bacterial Toxins in the Lungs.细菌毒素对肺部的影响。
Toxins (Basel). 2020 Apr 2;12(4):223. doi: 10.3390/toxins12040223.
3
Human monoclonal anti-protective antigen antibody for the low-dose post-exposure prophylaxis and treatment of Anthrax.用于炭疽低剂量暴露后预防和治疗的人源化抗保护性抗原单克隆抗体。
BMC Infect Dis. 2018 Dec 10;18(1):640. doi: 10.1186/s12879-018-3542-6.
4
Advances in structure determination by cryo-EM to unravel membrane-spanning pore formation.冷冻电镜结构测定技术在解析跨膜孔形成中的进展。
Protein Sci. 2018 Sep;27(9):1544-1556. doi: 10.1002/pro.3454.
5
Molecular assembly of lethal factor enzyme and pre-pore heptameric protective antigen in early stage of translocation.致死因子酶与七聚体前孔保护性抗原在转运早期的分子组装。
J Mol Model. 2016 Jan;22(1):7. doi: 10.1007/s00894-015-2878-8. Epub 2015 Dec 11.
6
An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.用于炭疽芽孢杆菌感染和败血症辅助治疗的研究性毒素导向疗法概述。
Expert Opin Investig Drugs. 2015;24(7):851-65. doi: 10.1517/13543784.2015.1041587. Epub 2015 Apr 28.
7
Channel-forming bacterial toxins in biosensing and macromolecule delivery.通道形成细菌毒素在生物传感和生物大分子递送中的应用。
Toxins (Basel). 2014 Aug 21;6(8):2483-540. doi: 10.3390/toxins6082483.
8
A protective antigen mutation increases the pH threshold of anthrax toxin receptor 2-mediated pore formation.一种保护性抗原突变提高了炭疽毒素受体2介导的孔形成的pH阈值。
Biochemistry. 2014 Apr 8;53(13):2166-71. doi: 10.1021/bi5000756. Epub 2014 Mar 25.
9
Designing inhibitors of anthrax toxin.炭疽毒素抑制剂的设计
Expert Opin Drug Discov. 2014 Mar;9(3):299-318. doi: 10.1517/17460441.2014.877884. Epub 2014 Jan 22.
10
(19)F nuclear magnetic resonance and crystallographic studies of 5-fluorotryptophan-labeled anthrax protective antigen and effects of the receptor on stability.5-氟色氨酸标记的炭疽保护性抗原的氟核磁共振和晶体学研究以及受体对稳定性的影响
Biochemistry. 2014 Feb 4;53(4):690-701. doi: 10.1021/bi401405s. Epub 2014 Jan 15.
本文引用的文献
1
The unfolding story of anthrax toxin translocation.炭疽毒素转位的展开故事。
Mol Microbiol. 2011 May;80(3):588-95. doi: 10.1111/j.1365-2958.2011.07614.x. Epub 2011 Mar 28.
2
Chemical dissection of protein translocation through the anthrax toxin pore.通过炭疽毒素孔道的蛋白质转运的化学剖析
Angew Chem Int Ed Engl. 2011 Mar 1;50(10):2294-6. doi: 10.1002/anie.201006460. Epub 2011 Feb 3.
3
Biogenesis of the pore architecture of a voltage-gated potassium channel.电压门控钾通道的孔结构的生物发生。
Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3240-5. doi: 10.1073/pnas.1017097108. Epub 2011 Feb 7.
4
Progress and novel strategies in vaccine development and treatment of anthrax.炭疽疫苗研发和治疗的进展和新策略。
Immunol Rev. 2011 Jan;239(1):221-36. doi: 10.1111/j.1600-065X.2010.00969.x.
5
Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers.炭疽致死因子被保护性抗原寡聚物展开的结构基础。
Nat Struct Mol Biol. 2010 Nov;17(11):1383-90. doi: 10.1038/nsmb.1923. Epub 2010 Oct 31.
6
Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin.包含β1 整合素的异二聚体整合素复合物促进炭疽毒素的内化和致死作用。
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15583-8. doi: 10.1073/pnas.1010145107. Epub 2010 Aug 16.
7
Evidence that histidine protonation of receptor-bound anthrax protective antigen is a trigger for pore formation.受体结合炭疽保护性抗原的组氨酸质子化是形成孔的触发因素的证据。
Biochemistry. 2010 Aug 24;49(33):6973-83. doi: 10.1021/bi100647z.
8
A femtomol range FRET biosensor reports exceedingly low levels of cell surface furin: implications for the processing of anthrax protective antigen.飞摩尔级 FRET 生物传感器报告极低水平的细胞表面弗林蛋白酶：对炭疽保护性抗原加工的影响。
PLoS One. 2010 Jun 24;5(6):e11305. doi: 10.1371/journal.pone.0011305.
9
Imaging the cell entry of the anthrax oedema and lethal toxins with fluorescent protein chimeras.用荧光蛋白嵌合体对炭疽水肿和致死毒素的细胞进入进行成像。
Cell Microbiol. 2010 Oct;12(10):1435-45. doi: 10.1111/j.1462-5822.2010.01480.x.
10
Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma.保护性抗原八聚体在炭疽致死毒素在血浆中稳定化的分子机制中的作用。
J Mol Biol. 2010 Jun 25;399(5):741-58. doi: 10.1016/j.jmb.2010.04.041. Epub 2010 Apr 28.
Zotero 插件