Suppr超能文献

三级接触中的远程扰动引发赖氨酸与细胞色素c中血红素铁的连接。

Remote Perturbations in Tertiary Contacts Trigger Ligation of Lysine to the Heme Iron in Cytochrome c.

作者信息

Gu Jie, Shin Dong-Woo, Pletneva Ekaterina V

机构信息

Department of Chemistry, Dartmouth College , Hanover, New Hampshire 03755, United States.

出版信息

Biochemistry. 2017 Jun 13;56(23):2950-2966. doi: 10.1021/acs.biochem.6b01187. Epub 2017 May 31.

Abstract

Perturbations in protein structure define the mechanism of allosteric regulation and biological information transfer. In cytochrome c (cyt c), ligation of Met80 to the heme iron is critical for the protein's electron-transfer (ET) function in oxidative phosphorylation and for suppressing its peroxidase activity in apoptosis. The hard base Lys is a better match for the hard ferric iron than the soft base Met is, suggesting the key role of the protein scaffold in favoring Met ligation. To probe the role of the protein structure in the maintenance of Met ligation, mutations T49V and Y67R/M80A were designed to disrupt hydrogen bonding and packing of the heme coordination loop, respectively. Electronic absorption, nuclear magnetic resonance, and electron paramagnetic resonance spectra reveal that ferric forms of both variants are Lys-ligated at neutral pH. A minor change in the tertiary contacts in T49V, away from the heme coordination loop, appears to be sufficient to execute a change in ligation, suggesting a cross-talk between the different regions of the protein structure and a possibility of built-in conformational switches in cyt c. Analyses of thermodynamic stability, kinetics of Lys binding and dissociation, and the pH-dependent changes in ligation provide a detailed characterization of the Lys coordination in these variants and relate these properties to the extent of structural perturbations. The findings emphasize the importance of the hydrogen-bonding network in controlling ligation of the native Met80 to the heme iron.

摘要

蛋白质结构的扰动决定了变构调节和生物信息传递的机制。在细胞色素c(cyt c)中,Met80与血红素铁的连接对于该蛋白质在氧化磷酸化中的电子传递(ET)功能以及在细胞凋亡中抑制其过氧化物酶活性至关重要。硬碱赖氨酸比软碱甲硫氨酸更适合与硬铁离子结合,这表明蛋白质支架在促进甲硫氨酸连接方面的关键作用。为了探究蛋白质结构在维持甲硫氨酸连接中的作用,设计了突变T49V和Y67R/M80A,分别破坏血红素配位环的氢键和堆积。电子吸收、核磁共振和电子顺磁共振光谱表明,在中性pH条件下,两种变体的铁离子形式均与赖氨酸连接。T49V中远离血红素配位环的三级接触的微小变化似乎足以导致连接变化,这表明蛋白质结构的不同区域之间存在相互作用,并且cyt c中存在内在构象开关的可能性。对热力学稳定性、赖氨酸结合和解离动力学以及连接的pH依赖性变化的分析详细表征了这些变体中赖氨酸的配位情况,并将这些性质与结构扰动程度相关联。这些发现强调了氢键网络在控制天然Met80与血红素铁连接中的重要性。

相似文献

1
Remote Perturbations in Tertiary Contacts Trigger Ligation of Lysine to the Heme Iron in Cytochrome c.
Biochemistry. 2017 Jun 13;56(23):2950-2966. doi: 10.1021/acs.biochem.6b01187. Epub 2017 May 31.
3
A Heme Propionate Staples the Structure of Cytochrome for Methionine Ligation to the Heme Iron.
Inorg Chem. 2019 Oct 21;58(20):14085-14106. doi: 10.1021/acs.inorgchem.9b02111. Epub 2019 Oct 7.
4
Ligation and Reactivity of Methionine-Oxidized Cytochrome c.
Inorg Chem. 2018 May 21;57(10):5754-5766. doi: 10.1021/acs.inorgchem.8b00010. Epub 2018 Apr 30.
6
Effect of methionine80 heme coordination on domain swapping of cytochrome c.
J Biol Inorg Chem. 2017 Jul;22(5):705-712. doi: 10.1007/s00775-017-1446-3. Epub 2017 Feb 28.
8
A model for the misfolded bis-His intermediate of cytochrome c: the 1-56 N-fragment.
J Inorg Biochem. 2004 Jun;98(6):1067-77. doi: 10.1016/j.jinorgbio.2004.02.026.

引用本文的文献

1
Disabling the Entatic Control of Methionine Ligation through Additive Destabilization of Ferric Cytochrome .
Inorg Chem. 2025 Jun 23;64(24):11966-11980. doi: 10.1021/acs.inorgchem.5c00839. Epub 2025 Jun 11.
2
Chemoselective Caging of Carboxyl Groups for On-Demand Protein Activation with Small Molecules.
Angew Chem Int Ed Engl. 2023 May 22;62(22):e202215614. doi: 10.1002/anie.202215614. Epub 2023 Apr 25.
3
NMR Reveals the Conformational Changes of Cytochrome C upon Interaction with Cardiolipin.
Life (Basel). 2021 Sep 30;11(10):1031. doi: 10.3390/life11101031.
4
A Heme Propionate Staples the Structure of Cytochrome for Methionine Ligation to the Heme Iron.
Inorg Chem. 2019 Oct 21;58(20):14085-14106. doi: 10.1021/acs.inorgchem.9b02111. Epub 2019 Oct 7.
5
Lysine carbonylation is a previously unrecognized contributor to peroxidase activation of cytochrome by chloramine-T.
Chem Sci. 2019 Jan 7;10(8):2349-2359. doi: 10.1039/c8sc03624a. eCollection 2019 Feb 28.
6
The K79G Mutation Reshapes the Heme Crevice and Alters Redox Properties of Cytochrome c.
Biochemistry. 2018 Oct 9;57(40):5827-5840. doi: 10.1021/acs.biochem.8b00650. Epub 2018 Sep 24.
7
Ligation and Reactivity of Methionine-Oxidized Cytochrome c.
Inorg Chem. 2018 May 21;57(10):5754-5766. doi: 10.1021/acs.inorgchem.8b00010. Epub 2018 Apr 30.
8
Histidine-Lysine Axial Ligand Switching in a Hemoglobin: A Role for Heme Propionates.
Biochemistry. 2018 Feb 6;57(5):631-644. doi: 10.1021/acs.biochem.7b01155. Epub 2018 Jan 10.
9
Design of artificial metalloproteins/metalloenzymes by tuning noncovalent interactions.
J Biol Inorg Chem. 2018 Jan;23(1):7-25. doi: 10.1007/s00775-017-1506-8. Epub 2017 Dec 7.

本文引用的文献

2
Lower Protein Stability Does Not Necessarily Increase Local Dynamics.
Biochemistry. 2016 May 17;55(19):2681-93. doi: 10.1021/acs.biochem.5b01060. Epub 2016 May 4.
3
Disruption of a hydrogen bond network in human versus spider monkey cytochrome c affects heme crevice stability.
J Inorg Biochem. 2016 May;158:62-69. doi: 10.1016/j.jinorgbio.2015.12.025. Epub 2015 Dec 31.
4
Structure-function relationships in human cytochrome c: The role of tyrosine 67.
J Inorg Biochem. 2016 Feb;155:56-66. doi: 10.1016/j.jinorgbio.2015.11.011. Epub 2015 Nov 12.
7
Structural basis for cytochrome c Y67H mutant to function as a peroxidase.
PLoS One. 2014 Sep 11;9(9):e107305. doi: 10.1371/journal.pone.0107305. eCollection 2014.
8
Structure of a mitochondrial cytochrome c conformer competent for peroxidase activity.
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6648-53. doi: 10.1073/pnas.1323828111. Epub 2014 Apr 23.
9
Control of cytochrome c redox reactivity through off-pathway modifications in the protein hydrogen-bonding network.
Chem Commun (Camb). 2014 May 25;50(40):5355-7. doi: 10.1039/c3cc47943a. Epub 2014 Jan 10.
10
Redox-dependent stability, protonation, and reactivity of cysteine-bound heme proteins.
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):E306-15. doi: 10.1073/pnas.1317173111. Epub 2014 Jan 7.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验