The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase
2017-01-31
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Status已发表
DOI10.1038/srep41882
AbstractHuman 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.
Indexed BySCI
Language英语
Funding ProjectChinese Academy of Sciences[XDB08010302]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000393082000001
PublisherNATURE PUBLISHING GROUP
WOS KeywordAMINO-ACID-SEQUENCES ; PIG-HEART ; BOVINE HEART ; MOLECULAR-CLONING ; MANGANOUS ION ; BINDING-SITES ; ADP ; IDENTIFICATION ; PURIFICATION ; MUTATIONS
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1526
Collection生命科学与技术学院_特聘教授组_丁建平组
Corresponding AuthorDing, Jianping
Affiliation
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
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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).
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