三甲胺 N-氧化物（TMAO）的质子化对于稳定 RNA 的三级结构是必需的。
Protonation of trimethylamine N-oxide (TMAO) is required for stabilization of RNA tertiary structure.
机构信息
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
出版信息
Biophys Chem. 2013 Dec 31;184:8-16. doi: 10.1016/j.bpc.2013.08.002. Epub 2013 Aug 17.
Abstract
The osmolyte trimethylamine N-oxide (TMAO) stabilizes the tertiary but not the secondary structures of RNA. However, molecular dynamics simulations performed on the PreQ1 riboswitch showed that TMAO destabilizes the tertiary riboswitch structure, leading us to hypothesize that the presence of RNA could result in enhanced population of the protonated form, TMAOP. Constant pH replica exchange simulations showed that a percentage of TMAO is indeed protonated, thus contributing to the stability of the tertiary but not the secondary structure of PreQ1. TMAOP results in an unfavorable dehydration of phosphodiester backbone, which is compensated by electrostatic attraction between TMAOP and the phosphate groups. In addition, TMAOP interacts with specific sites in the tertiary RNA structure, mimicking the behavior of positively charged ions and of the PreQ1 ligand in stabilizing RNA. Finally, we predict that TMAO-induced stabilization of RNA tertiary structures should be strongly pH dependent.
摘要
渗透调节剂三甲胺 N-氧化物（TMAO）稳定 RNA 的三级结构而非二级结构。然而，对 PreQ1 核糖开关进行的分子动力学模拟表明 TMAO 会破坏三级核糖开关结构，这使我们假设 RNA 的存在可能导致质子化形式 TMAOP 的丰度增加。恒 pH 复制交换模拟表明 TMAO 确实有一定比例质子化，从而有助于 PreQ1 的三级结构而非二级结构的稳定性。TMAOP 导致磷酸二酯骨架的不利去水，这通过 TMAOP 与磷酸基团之间的静电吸引得到补偿。此外，TMAOP 与三级 RNA 结构中的特定部位相互作用，模拟了带正电荷的离子和 PreQ1 配体稳定 RNA 的行为。最后，我们预测 TMAO 诱导的 RNA 三级结构稳定性应强烈依赖于 pH 值。
相似文献
1
Protonation of trimethylamine N-oxide (TMAO) is required for stabilization of RNA tertiary structure.三甲胺 N-氧化物（TMAO）的质子化对于稳定 RNA 的三级结构是必需的。
Biophys Chem. 2013 Dec 31;184:8-16. doi: 10.1016/j.bpc.2013.08.002. Epub 2013 Aug 17.
2
The osmolyte TMAO stabilizes native RNA tertiary structures in the absence of Mg2+: evidence for a large barrier to folding from phosphate dehydration.渗透调节剂 TMAO 可在无 Mg2+ 的情况下稳定天然 RNA 的三级结构：来自于磷酸盐去水合作用的折叠大障碍的证据。
J Mol Biol. 2010 Nov 19;404(1):138-57. doi: 10.1016/j.jmb.2010.09.043. Epub 2010 Sep 25.
3
Trimethylamine N-oxide stabilizes RNA tertiary structure and attenuates the denaturating effects of urea.氧化三甲胺可稳定RNA三级结构并减弱尿素的变性作用。
J Am Chem Soc. 2003 Apr 16;125(15):4418-9. doi: 10.1021/ja0292997.
4
TMAO Destabilizes RNA Secondary Structure via Direct Hydrogen Bond Interactions.氧化三甲胺通过直接氢键相互作用破坏RNA二级结构。
J Phys Chem B. 2023 Jan 19;127(2):438-445. doi: 10.1021/acs.jpcb.2c05434. Epub 2023 Jan 5.
5
Effects of trimethylamine N-oxide (TMAO) and crowding agents on the stability of RNA hairpins.氧化三甲胺（TMAO）和拥挤剂对RNA发夹结构稳定性的影响。
J Am Chem Soc. 2008 Jun 11;130(23):7364-72. doi: 10.1021/ja078326w. Epub 2008 May 15.
6
Counteracting osmolyte trimethylamine N-oxide destabilizes proteins at pH below its pKa. Measurements of thermodynamic parameters of proteins in the presence and absence of trimethylamine N-oxide.抗渗透压剂三甲胺 N-氧化物在 pH 低于其 pKa 时会使蛋白质不稳定。在有和没有三甲胺 N-氧化物存在的情况下对蛋白质热力学参数的测量。
J Biol Chem. 2005 Mar 25;280(12):11035-42. doi: 10.1074/jbc.M410716200. Epub 2005 Jan 14.
7
Preventing misfolding of the prion protein by trimethylamine N-oxide.通过三甲胺 N-氧化物防止朊病毒蛋白错误折叠。
Biochemistry. 2004 Oct 19;43(41):12955-63. doi: 10.1021/bi0486379.
8
Counteraction of urea by trimethylamine N-oxide is due to direct interaction.三甲基胺 N-氧化物对尿素的拮抗作用是由于直接相互作用。
Biophys J. 2009 Nov 4;97(9):2559-66. doi: 10.1016/j.bpj.2009.08.017.
9
The osmolyte trimethylamine-N-oxide stabilizes the Fyn SH3 domain without altering the structure of its folding transition state.渗透溶质三甲胺 - N - 氧化物可稳定Fyn SH3结构域，而不改变其折叠过渡态的结构。
Protein Sci. 2009 Mar;18(3):526-36. doi: 10.1002/pro.52.
10
Microscopic stability of cold shock protein A examined by NMR native state hydrogen exchange as a function of urea and trimethylamine N-oxide.通过核磁共振天然态氢交换研究冷休克蛋白A在尿素和三甲胺N-氧化物作用下的微观稳定性。
Protein Sci. 2000 Feb;9(2):290-301. doi: 10.1110/ps.9.2.290.
引用本文的文献
1
Single-molecule FRET observes opposing effects of urea and TMAO on structurally similar meso- and thermophilic riboswitch RNAs.单分子 FRET 观察到脲和 TMAO 对结构相似的中温和嗜热核糖开关 RNA 产生相反的影响。
Nucleic Acids Res. 2023 Nov 10;51(20):11345-11357. doi: 10.1093/nar/gkad866.
2
Solutions: how adaptive changes in cellular fluids enable marine life to cope with abiotic stressors.解决方案：细胞液中的适应性变化如何使海洋生物应对非生物应激源。
Mar Life Sci Technol. 2022 Aug 16;4(3):389-413. doi: 10.1007/s42995-022-00140-3. eCollection 2022 Aug.
3
Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated By Trimethylamine-N-Oxide.Toll样受体4：一种巨噬细胞表面受体被氧化三甲胺激活。
Cell J. 2021 Oct;23(5):516-522. doi: 10.22074/cellj.2021.7849. Epub 2021 Oct 30.
4
Simultaneous quantification of trimethylamine N-oxide, trimethylamine, choline, betaine, creatinine, and propionyl-, acetyl-, and L-carnitine in clinical and food samples using HILIC-LC-MS.采用亲水作用色谱-液相色谱-串联质谱法同时定量检测临床和食品样本中的氧化三甲胺、三甲胺、胆碱、甜菜碱、肌酐以及丙酰基、乙酰基和左旋肉碱。
Anal Bioanal Chem. 2021 Sep;413(21):5349-5360. doi: 10.1007/s00216-021-03509-y. Epub 2021 Jul 13.
5
The remodel of the "central dogma": a metabolomics interaction perspective.“中心法则”的重塑：代谢组学相互作用视角。
Metabolomics. 2021 May 9;17(5):48. doi: 10.1007/s11306-021-01800-8.
6
Bridging the gap between in vitro and in vivo RNA folding.弥合体外与体内RNA折叠之间的差距。
Q Rev Biophys. 2016 Jan;49:e10. doi: 10.1017/S003358351600007X. Epub 2016 Jun 24.
7
DIRECT-ID: An automated method to identify and quantify conformational variations--application to β2 -adrenergic GPCR.直接鉴定法：一种用于识别和量化构象变化的自动化方法——应用于β2 -肾上腺素能G蛋白偶联受体
J Comput Chem. 2016 Feb 5;37(4):416-25. doi: 10.1002/jcc.24231. Epub 2015 Nov 12.
8
Structure and function of preQ riboswitches.preQ核糖开关的结构与功能。
Biochim Biophys Acta. 2014 Oct;1839(10):939-950. doi: 10.1016/j.bbagrm.2014.04.019. Epub 2014 May 4.
本文引用的文献
1
pH-dependent dynamics of complex RNA macromolecules.复杂RNA大分子的pH依赖性动力学
J Chem Theory Comput. 2013 Feb 12;9(2):935-943. doi: 10.1021/ct300942z. Epub 2013 Jan 3.
2
Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape.对抗化学伴侣对单分子α-突触核蛋白结构景观的影响。
Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):17826-31. doi: 10.1073/pnas.1201802109. Epub 2012 Jul 23.
3
Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent.在显式溶剂中核酸的恒pH分子动力学模拟
J Chem Theory Comput. 2012 Jan 10;8(1):36-46. doi: 10.1021/ct2006314.
4
Entropic stabilization of proteins by TMAO.三甲基胺 N-氧化物（TMAO）对蛋白质的熵稳定作用。
J Phys Chem B. 2011 Nov 17;115(45):13401-7. doi: 10.1021/jp207289b. Epub 2011 Oct 26.
5
Predicting pKa values with continuous constant pH molecular dynamics.利用连续恒定pH值分子动力学预测pKa值
Methods Enzymol. 2009;466:455-75. doi: 10.1016/S0076-6879(09)66019-5. Epub 2009 Nov 13.
6
MDAnalysis: a toolkit for the analysis of molecular dynamics simulations.MDAnalysis：一个用于分析分子动力学模拟的工具包。
J Comput Chem. 2011 Jul 30;32(10):2319-27. doi: 10.1002/jcc.21787. Epub 2011 Apr 15.
7
Impact of 2'-hydroxyl sampling on the conformational properties of RNA: update of the CHARMM all-atom additive force field for RNA.2'-羟基采样对 RNA 构象性质的影响：RNA 的 CHARMM 全原子加和力场的更新。
J Comput Chem. 2011 Jul 15;32(9):1929-43. doi: 10.1002/jcc.21777. Epub 2011 Apr 5.
8
Comparison of solution and crystal structures of preQ1 riboswitch reveals calcium-induced changes in conformation and dynamics.比较 preQ1 核糖开关的溶液和晶体结构揭示了钙诱导构象和动力学变化。
J Am Chem Soc. 2011 Apr 13;133(14):5190-3. doi: 10.1021/ja111769g. Epub 2011 Mar 16.
9
The osmolyte TMAO stabilizes native RNA tertiary structures in the absence of Mg2+: evidence for a large barrier to folding from phosphate dehydration.渗透调节剂 TMAO 可在无 Mg2+ 的情况下稳定天然 RNA 的三级结构：来自于磷酸盐去水合作用的折叠大障碍的证据。
J Mol Biol. 2010 Nov 19;404(1):138-57. doi: 10.1016/j.jmb.2010.09.043. Epub 2010 Sep 25.
10
Dependence of RNA tertiary structural stability on Mg2+ concentration: interpretation of the Hill equation and coefficient.RNA 三级结构稳定性对 Mg2+ 浓度的依赖性：Hill 方程和系数的解释。
Biochemistry. 2010 Mar 9;49(9):1843-53. doi: 10.1021/bi902036j.
Zotero 插件