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| The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases | |
| 2021-03-18 | |
| Source Publication | NUCLEIC ACIDS RESEARCH
 |
| ISSN | 0305-1048 |
| EISSN | 1362-4962 |
| Volume | 49Issue:5Pages:2816-2834 |
| DOI | 10.1093/nar/gkab104 |
| Abstract | GTPBP3 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. |
| URL | 查看原文 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| WOS ID | WOS:000637321700033 |
| Publisher | OXFORD UNIV PRESS |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://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 |
| Corresponding Author | Wang, En-Duo; Zhou, Xiao-Long |
| Affiliation | 1.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 Affilication | School of Life Science and Technology |
| Corresponding Author Affilication | School 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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