Ubiquitin is a carbon dioxide-binding protein.

Ubiquitin is a carbon dioxide-binding protein.
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泛素是一种二氧化碳结合蛋白。

DOI:
10.1126/sciadv.abi5507
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发表时间:
2021-09-24
期刊:
影响因子:
13.6
通讯作者:
Cann MJ
Cann MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Linthwaite VL;Pawloski W;Pegg HB;Townsend PD;Thomas MJ;So VKH;Brown AP;Hodgson DRW;Lorimer GH;Fushman D;Cann MJ

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改变的泛素结合是哺乳动物细胞对波动的pCO 2作出反应的一种机制。CO2结合蛋白的鉴定对于理解CO2调节的分子过程至关重要。CO2可以通过中性N-末端α-氨基或赖氨酸ε-氨基的氨甲酰化形成可逆的翻译后修饰。我们以前已经开发了三乙基氧铵(TEO)离子作为化学蛋白质组学工具共价捕获的氨基甲酸酯,在这里,我们部署TEO确定泛素作为哺乳动物CO2结合蛋白。我们使用13 C-NMR光谱来证明CO2在泛素N末端和赖氨酸6、33、48和63的ε-氨基上形成氨基甲酸酯。我们证明了生物学相关的pCO 2水平降低了泛素在赖氨酸-48处的结合,并下调了泛素依赖的NF-κB途径的激活。我们的研究结果表明,泛素是一种CO2结合蛋白,并证明氨甲酰化作为一种可行的机制,哺乳动物细胞可以响应波动pCO 2。
Altered ubiquitin conjugation is a mechanism by which mammalian cells can respond to fluctuating pCO2. The identification of CO2-binding proteins is crucial to understanding CO2-regulated molecular processes. CO2 can form a reversible posttranslational modification through carbamylation of neutral N-terminal α-amino or lysine ε-amino groups. We have previously developed triethyloxonium (TEO) ion as a chemical proteomics tool for covalent trapping of carbamates, and here, we deploy TEO to identify ubiquitin as a mammalian CO2-binding protein. We use 13C-NMR spectroscopy to demonstrate that CO2 forms carbamates on the ubiquitin N terminus and ε-amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant pCO2 levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-κB pathway activation. Our results show that ubiquitin is a CO2-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating pCO2.
DOI: 10.1073/pnas.1711017115
发表时间: 2018-05-01
影响因子: 11.1
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发表时间: 2015-07
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