气候变化领域集成服务门户(CCPortal): Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer

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DOI	10.1073/PNAS.2016717118
	Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer
	Sarkar A.; Carter E.L.; Harland J.B.; Speelman A.L.; Lehnert N.; Ragsdale S.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Rev-Erbβ is a nuclear receptor that couples circadian rhythm, metabolism, and inflammation. Heme binding to the protein modulates its function as a repressor, its stability, its ability to bind other proteins, and its activity in gas sensing. Rev-Erbβ binds Fe3+-heme more tightly than Fe2+-heme, suggesting its activities may be regulated by the heme redox state. Yet, this critical role of heme redox chemistry in defining the protein's resting state and function is unknown. We demonstrate by electrochemical and whole-cell electron paramagnetic resonance experiments that Rev-Erbβ exists in the Fe3+ form within the cell allowing the protein to be heme replete even at low concentrations of labile heme in the nucleus. However, being in the Fe3+ redox state contradicts Rev-Erb's known function as a gas sensor, which dogma asserts must be Fe2+. This paper explains why the resting Fe3+ state is congruent both with heme binding and cellular gas sensing. We show that the binding of CO/NO elicits a striking increase in the redox potential of the Fe3+/ Fe2+ couple, characteristic of an EC mechanism in which the unfavorable Electrochemical reduction of heme is coupled to the highly favorable Chemical reaction of gas binding, making the reduction spontaneous. Thus, Fe3+-Rev-Erbβ remains heme-loaded, crucial for its repressor activity, and undergoes reduction when diatomic gases are present. This work has broad implications for proteins in which ligand-triggered redox changes cause conformational changes influencing its function or interprotein interactions (e.g., between NCoR1 and Rev-Erbβ). This study opens up the possibility of CO/ NO-mediated regulation of the circadian rhythm through redox changes in Rev-Erbβ. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Electro-chemical coupling; Heme; Redox; Rev-Erb
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181020
作者单位	Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, United States; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, United States; Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Sarkar A.,Carter E.L.,Harland J.B.,et al. Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer[J],2021,118(3).
APA	Sarkar A.,Carter E.L.,Harland J.B.,Speelman A.L.,Lehnert N.,&Ragsdale S.W..(2021).Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Sarkar A.,et al."Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).