The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases
Peng, Gui-Xin1,2; Zhang, Yong1; Wang, Qin-Qin2; Li, Qing-Run3; Xu, Hong4; Wang, En-Duo1,2; Zhou, Xiao-Long1
2021
Source PublicationNUCLEIC ACIDS RESEARCH
ISSN0305-1048
EISSN1362-4962
Volume49Issue:5Pages:2816-2834
DOI10.1093/nar/gkab104
AbstractGTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (tau m(5)U) biosynthesis at the 34(th) wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing tau m(5)U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of tau m(5)U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high K-m values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the tau m(5)U modification mechanism and etiology of tau m(5)U deficiency-related diseases.
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Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000637321700033
PublisherOXFORD UNIV PRESS
Original Document TypeArticle
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126815
Collection生命科学与技术学院_博士生
生命科学与技术学院_特聘教授组_王恩多组
生命科学与技术学院_硕士生
信息科学与技术学院_博士生
Affiliation1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, 320 Yue Yang Rd, Shanghai 200031, Peoples R China;
2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Hua Xia Rd, Shanghai 201210, Peoples R China;
3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, CAS Key Lab Syst Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China;
4.Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Shanghai Municipal Key Clin Specialty, Shanghai Key Lab Embryo Original Dis,Sch Med, 910 Heng Shan Rd, Shanghai 200030, Peoples R China
First Author AffilicationSchool of Life Science and Technology
Recommended Citation
GB/T 7714
Peng, Gui-Xin,Zhang, Yong,Wang, Qin-Qin,et al. The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases[J]. NUCLEIC ACIDS RESEARCH,2021,49(5):2816-2834.
APA Peng, Gui-Xin.,Zhang, Yong.,Wang, Qin-Qin.,Li, Qing-Run.,Xu, Hong.,...&Zhou, Xiao-Long.(2021).The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases.NUCLEIC ACIDS RESEARCH,49(5),2816-2834.
MLA Peng, Gui-Xin,et al."The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases".NUCLEIC ACIDS RESEARCH 49.5(2021):2816-2834.
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