气体信号分子的血红素蛋白靶点研究进展

doi:10.19586/j.2095-2341.2023.0044

生物技术进展 ›› 2023, Vol. 13 ›› Issue (4): 499-508.DOI: 10.19586/j.2095-2341.2023.0044

• 进展评述 • 上一篇

气体信号分子的血红素蛋白靶点研究进展

李骏, 宋怡菲, 仪杨, 马晨, 张黄子怡, 杜琳琳, 李峻宇, 谢飞(), 马雪梅()

北京工业大学环境与生命学部，北京 100124

收稿日期:2023-03-31 接受日期:2023-05-04 出版日期:2023-07-25 发布日期:2023-08-03
通讯作者: 谢飞,马雪梅
作者简介:第一联系人：李俊E-mail: Lijun199907@163.com
基金资助:
军委后勤保障部开放研究重点项目(BHJ17L018)

Research Progress on Heme Protein Targets of Gas Signaling Molecules

Jun LI, Yifei SONG, Yang YI, Chen MA, Ziyi ZHANG⁃HUANG, Linlin DU, Junyu LI, Fei XIE(), Xuemei MA()

Faculty of Environment and Life，Beijing University of Technology，Beijing 100124，China

Received:2023-03-31 Accepted:2023-05-04 Online:2023-07-25 Published:2023-08-03
Contact: Fei XIE,Xuemei MA

摘要/Abstract

摘要：

气体信号分子包括一氧化氮、一氧化碳和硫化氢等，在调节血管扩张、神经传递、血小板凝集、免疫、细胞增殖和线粒体呼吸等生理过程中起着至关重要的作用。已有研究表明细胞中的血红素蛋白是气体信号分子的主要受体之一，它们都有共同的辅因子——血红素。血红素由4个吡咯类亚基组成的环状结构，中心螯合了1个亚铁离子的基团，是血红蛋白、肌红蛋白、过氧化物酶、细胞色素等蛋白质的辅基，中间的亚铁离子可以和气体信号分子配位结合，广泛地参与生物体内各项生理活动。对气体信号分子作用的血红素蛋白种类以及下游通路进行了综述，以期为深入研究其作用机制提供参考。

关键词: 血红素蛋白, 一氧化氮, 一氧化碳, 硫化氢, 氢气

Abstract:

Gas signaling molecules， including nitric oxide， carbon monoxide， and hydrogen sulfide， play crucial roles in regulating physiological processes such as vasodilation， neurotransmission， platelet aggregation， immunity， cell proliferation， and mitochondrial respiration. Studies have shown that heme protein in cells is one of the main receptors of gas signal molecules， and they all have the same cofactor—heme. Heme is a ring composed of four pyrrole subunits， with a center chelating a ferrous ion group. It is a co-group of proteins such as hemoglobin， myoglobin， peroxidase and cytochrome. The intermediate ferrous ion can coordinate and bind with gas signaling molecules， widely participating in various physiological activities of organisms. In this paper， the types of heme proteins and downstream pathways involved in the action of gas signaling molecules were reviewed， with a view to providing reference for further study of their mechanisms.

Key words: heme sensors, nitric oxide, carbon monoxide, hydrogen sulfide, hydrogen

中图分类号:

李骏, 宋怡菲, 仪杨, 马晨, 张黄子怡, 杜琳琳, 李峻宇, 谢飞, 马雪梅. 气体信号分子的血红素蛋白靶点研究进展[J]. 生物技术进展, 2023, 13(4): 499-508.

Jun LI, Yifei SONG, Yang YI, Chen MA, Ziyi ZHANG⁃HUANG, Linlin DU, Junyu LI, Fei XIE, Xuemei MA. Research Progress on Heme Protein Targets of Gas Signaling Molecules[J]. Current Biotechnology, 2023, 13(4): 499-508.

图/表 8

参考文献 69

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蛋白名称	参与的生理学过程	蛋白分布情况	发挥作用的方式
CLOCK/BMAL1异源二聚体	调节生物体节律	哺乳动物	通过蛋白质之间相互作用
组氨酸激酶	调节细菌休眠	细菌	通过磷酸化的传递
鸟苷酸环化酶	调控血管内壁压力	哺乳动物	通过胞内信使传导信号
血红蛋白、肌红蛋白	负责在体内运输氧气	动物	通过血红素中的铁离子可逆结合
细胞色素类蛋白	负责传递电子，参与生物氧化	动物、植物	通过血红素中铁离子的还原态和氧化态之间的可逆变化

蛋白名称	参与的生理学过程	蛋白分布情况	发挥作用的方式
CLOCK/BMAL1异源二聚体	调节生物体节律	哺乳动物	通过蛋白质之间相互作用
组氨酸激酶	调节细菌休眠	细菌	通过磷酸化的传递
鸟苷酸环化酶	调控血管内壁压力	哺乳动物	通过胞内信使传导信号
血红蛋白、肌红蛋白	负责在体内运输氧气	动物	通过血红素中的铁离子可逆结合
细胞色素类蛋白	负责传递电子，参与生物氧化	动物、植物	通过血红素中铁离子的还原态和氧化态之间的可逆变化

气体信号分子	结合的血红素蛋白	结合位点	如何诱导构象变化	产生的生理功能
NO	鸟苷酸环化酶(sGC)	血红素中的Fe²⁺	2个亚基的催化结构域之间发生了扭转，底物结合口袋打开，并催化GTP形成cGMP	激活sGC活性，调节生物体血压
	血红素一氧化氮/氧结合蛋白(H⁃NOX)	血红素中的Fe²⁺	引起蛋白质N端半部分的移位，导致H⁃NOX整体的构象发生变化	调控细菌生物膜形成
	NO敏感蛋白(NosP)	血红素中的Fe²⁺	未知	调控细菌生物膜扩散
CO	sGC	血红素中的Fe²⁺	2个亚基的催化结构域之间发生了扭转，底物结合口袋打开，并催化GTP形成cGMP	激活sGC活性
	CO氧化激活剂(CooA)	血红素中的Fe²⁺	N末端经过大的重新定位	激活负责CO氧化的酶转录
	RcoM	血红素中的Fe²⁺	未知	参与细菌内CO氧化功能
	胱硫醚β⁃合酶(CBS)	血红素中的Fe²⁺	未知	抑制CBS活性
H₂S	未发现	未知	未知	动物：舒张血管、降低血压；植物：调节气孔运动、促进根的发育、种子萌发、光合作用等

气体信号分子	结合的血红素蛋白	结合位点	如何诱导构象变化	产生的生理功能
NO	鸟苷酸环化酶(sGC)	血红素中的Fe²⁺	2个亚基的催化结构域之间发生了扭转，底物结合口袋打开，并催化GTP形成cGMP	激活sGC活性，调节生物体血压
	血红素一氧化氮/氧结合蛋白(H⁃NOX)	血红素中的Fe²⁺	引起蛋白质N端半部分的移位，导致H⁃NOX整体的构象发生变化	调控细菌生物膜形成
	NO敏感蛋白(NosP)	血红素中的Fe²⁺	未知	调控细菌生物膜扩散
CO	sGC	血红素中的Fe²⁺	2个亚基的催化结构域之间发生了扭转，底物结合口袋打开，并催化GTP形成cGMP	激活sGC活性
	CO氧化激活剂(CooA)	血红素中的Fe²⁺	N末端经过大的重新定位	激活负责CO氧化的酶转录
	RcoM	血红素中的Fe²⁺	未知	参与细菌内CO氧化功能
	胱硫醚β⁃合酶(CBS)	血红素中的Fe²⁺	未知	抑制CBS活性
H₂S	未发现	未知	未知	动物：舒张血管、降低血压；植物：调节气孔运动、促进根的发育、种子萌发、光合作用等

细菌名称	拉丁文名	NosP种类	氨基酸数目	结合血红素数目	是否含有H⁃NOX
铜绿假单胞菌	Pseudomonas aeruginosa	1	387	1	否
霍乱弧菌	Vibrio cholerae	2	405/395	1/1	否
希瓦氏菌	Shewanella oneidensis	1	395	1	否
嗜肺军团菌	Legionella pneumophila	1	388	1	是

气体信号分子的血红素蛋白靶点研究进展

Research Progress on Heme Protein Targets of Gas Signaling Molecules

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名称	拉丁文名	呼吸类型	含有RcoM的种类	生理功能
艾氏碱菌	Alcinella ehrlichei	需氧	1	参与CO氧化功能
异种伯克霍尔德菌	Burkholderia xenovorans	需氧	2	参与CO氧化功能
皮氏地杆菌	Geobacter sp. strain FRC⁃32	厌氧	1	参与CO氧化功能
硫还原土杆菌	Geobacterium sulfurreducens	厌氧	1	参与CO氧化功能
还原铀地杆菌	G. uraniumreducens	厌氧	1	参与CO氧化功能
甲醇假单胞菌	Pseudomonas carbinolinicus	厌氧	1	参与CO氧化功能
茎瘤固氮根瘤菌	Azorhizobium caulinodans	需氧	1	功能未知
自养黄杆菌	Xanthobacter autotrophicus	需氧	1	功能未知
磁性磁螺菌	Magnetospirillum magneticum	兼性厌氧	1	功能未知
格瑞菲斯瓦尔德磁螺菌	Magnetospirillum magnetotacticum	兼性厌氧	1	功能未知
磁螺菌	Magnetospirillum gryphiswaldense	兼性厌氧	1	功能未知
深红红螺菌	Rhodospirillum rubrum	厌氧	1	功能未知

蛋白名称	结构组成	结合血红素数	生理功能	CO作用
血红蛋白	2个α亚基和2个β亚基组成异二聚体	4	运输生物体内氧气和二氧化碳	与氧气竞争血红素的结合位点，使血红蛋白失去运输氧气的能力
肌红蛋白	球形/单条肽链	1	细胞内储存和分配氧气	与氧气竞争影响肌细胞内供氧
血红素加氧酶⁃1	单条肽链	1	负责生物体内血红素分解的诱导酶，并产生CO	未知
一氧化氮合酶	二聚体	1	在体内催化L⁃精氨酸生成NO	通过钙和磷脂酰肌醇3⁃激酶/Akt机制激活一氧化氮合酶
细胞色素C	球形/单条肽链	1	在线粒体嵴上与其他氧化酶排列成呼吸链，传递电子	抑制细胞色素C功能，直接抑制细胞内呼吸
细胞色素P450	单条肽链	1	参与生物合成和许多生理有效物质的代谢	抑制细胞色素P450活性

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