The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase

doi:10.1038/srep41882

	The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase
	Ma, Tengfei 1; Peng, Yingjie 1; Huang, Wei 1; Liu, Yabing 2; Ding, Jianping1,3,4,5
	2017-01-31
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	7
发表状态	已发表
DOI	10.1038/srep41882
摘要	Human NAD-dependent isocitrate dehydrogenase existing as the alpha(2)beta gamma heterotetramer, catalyzes the decarboxylation of isocitrate into a-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory beta and gamma subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing alpha beta and alpha gamma heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that alpha beta and alpha gamma alone have considerable basal activity but the full activity of alpha(2)beta gamma requires the assembly and cooperative function of both heterodimers. alpha(2)beta gamma and alpha gamma can be activated by citrate or/and ADP, whereas alpha beta cannot. The binding of citrate or/and ADP decreases the S-0.5,S- isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate alpha(2)beta gamma and alpha gamma at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on alpha beta. Furthermore, the allosteric activation of alpha(2)beta gamma is through the. subunit not the gamma subunit. These results demonstrate that the. subunit plays regulatory role to activate the holoenzyme, and the gamma subunit the structural role to facilitate the assembly of the holoenzyme.
收录类别	SCI
语种	英语
资助项目	Chinese Academy of Sciences[XDB08010302]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000393082000001
出版者	NATURE PUBLISHING GROUP
WOS关键词	AMINO-ACID-SEQUENCES ; PIG-HEART ; BOVINE HEART ; MOLECULAR-CLONING ; MANGANOUS ION ; BINDING-SITES ; ADP ; IDENTIFICATION ; PURIFICATION ; MUTATIONS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1526
专题	生命科学与技术学院_特聘教授组_丁建平组
通讯作者	Ding, Jianping
作者单位	1.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol,Shanghai Inst Biol Sci, Ctr Excellence Mol Cell Sci,Inst Biochem & Cell B, 320 Yueyang Rd, Shanghai 200031, Peoples R China 2.Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 4.Chinese Acad Sci, Shanghai Sci Res Ctr, 333 Haike Rd, Shanghai 201210, Peoples R China 5.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, 2005 Songhu Rd, Shanghai 200438, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Ma, Tengfei,Peng, Yingjie,Huang, Wei,et al. The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase[J]. SCIENTIFIC REPORTS,2017,7.
APA	Ma, Tengfei,Peng, Yingjie,Huang, Wei,Liu, Yabing,&Ding, Jianping.(2017).The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase.SCIENTIFIC REPORTS,7.
MLA	Ma, Tengfei,et al."The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase".SCIENTIFIC REPORTS 7(2017).