Pub Date : 2024-09-17DOI: 10.1038/s41422-024-01033-z
Zuodong Zhao, Bing Zhu
{"title":"Lysine methylation steps into another step of the central dogma","authors":"Zuodong Zhao, Bing Zhu","doi":"10.1038/s41422-024-01033-z","DOIUrl":"https://doi.org/10.1038/s41422-024-01033-z","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1038/s41422-024-01032-0
Nai-Qian Dong, Hong-Xuan Lin
{"title":"tRNA repair: the key to thermo-sensitive male sterility in rice","authors":"Nai-Qian Dong, Hong-Xuan Lin","doi":"10.1038/s41422-024-01032-0","DOIUrl":"https://doi.org/10.1038/s41422-024-01032-0","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1038/s41422-024-01029-9
Haiyan Liu
{"title":"Designing de novo D-protein binders","authors":"Haiyan Liu","doi":"10.1038/s41422-024-01029-9","DOIUrl":"https://doi.org/10.1038/s41422-024-01029-9","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1038/s41422-024-01026-y
Weibin Liu,Yan Li,George P Patrinos,Shuhua Xu,Meow-Keong Thong,Zhengming Chen,Francis P Crawley,Liming Li,Perihan Elif Ekmekci,Radoje Drmanac,Weiyang Cheong,Robert Benamouzig,Quan Nguyen,Pavel Volchkov,Juergen K V Reichardt,Piero Carninci,Partha Majumder,Xin Jin,George Church,Jian Wang,Xun Xu
{"title":"The 1% gift to humanity: The Human Genome Project II.","authors":"Weibin Liu,Yan Li,George P Patrinos,Shuhua Xu,Meow-Keong Thong,Zhengming Chen,Francis P Crawley,Liming Li,Perihan Elif Ekmekci,Radoje Drmanac,Weiyang Cheong,Robert Benamouzig,Quan Nguyen,Pavel Volchkov,Juergen K V Reichardt,Piero Carninci,Partha Majumder,Xin Jin,George Church,Jian Wang,Xun Xu","doi":"10.1038/s41422-024-01026-y","DOIUrl":"https://doi.org/10.1038/s41422-024-01026-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1038/s41422-024-01023-1
Yaxin Dai, Chia-Hsueh Lee
Urate is an endogenous product of purine metabolism in the liver. High urate levels in the blood lead to gout, a very common and painful inflammatory arthritis. Excreted urate is reabsorbed in the kidney mainly by URAT1 antiporter, a key target for anti-gout drugs. To uncover the mechanisms of urate transport and drug inhibition, we determined cryo-EM structures of human URAT1 with urate, counter anion pyrazinoate, or anti-gout drugs of different chemotypes - lesinurad, verinurad, and dotinurad. We captured the outward-to-inward transition of URAT1 during urate uptake, revealing that urate binds in a phenylalanine-rich pocket and engages with key gating residues to drive the transport cycle. In contrast to the single binding site for urate, pyrazinoate interacts with three distinct, functionally relevant sites within URAT1, a mechanism that has not yet been observed in other anion antiporters. In addition, we found that while all three drugs compete with substrates and halt the transport cycle, verinurad and dotinurad further hijack gating residues to achieve high potency. These insights advance our understanding of organic anion transport and provide a foundation for designing improved gout therapeutics.
{"title":"Transport mechanism and structural pharmacology of human urate transporter URAT1.","authors":"Yaxin Dai, Chia-Hsueh Lee","doi":"10.1038/s41422-024-01023-1","DOIUrl":"https://doi.org/10.1038/s41422-024-01023-1","url":null,"abstract":"<p><p>Urate is an endogenous product of purine metabolism in the liver. High urate levels in the blood lead to gout, a very common and painful inflammatory arthritis. Excreted urate is reabsorbed in the kidney mainly by URAT1 antiporter, a key target for anti-gout drugs. To uncover the mechanisms of urate transport and drug inhibition, we determined cryo-EM structures of human URAT1 with urate, counter anion pyrazinoate, or anti-gout drugs of different chemotypes - lesinurad, verinurad, and dotinurad. We captured the outward-to-inward transition of URAT1 during urate uptake, revealing that urate binds in a phenylalanine-rich pocket and engages with key gating residues to drive the transport cycle. In contrast to the single binding site for urate, pyrazinoate interacts with three distinct, functionally relevant sites within URAT1, a mechanism that has not yet been observed in other anion antiporters. In addition, we found that while all three drugs compete with substrates and halt the transport cycle, verinurad and dotinurad further hijack gating residues to achieve high potency. These insights advance our understanding of organic anion transport and provide a foundation for designing improved gout therapeutics.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1038/s41422-024-01012-4
Bin Yan, Chunyan Liu, Jing Sun, Yang Mao, Can Zhou, Ji Li, Wei Liu, Shengdong Li, Wei Yan, Chenjian Fu, Peng Qin, Xingxue Fu, Xinghui Zhao, Xianwei Song, Jiawei Nie, Feng Gao, Yuanzhu Yang, Yuhang Chen, Xiaofeng Cao
Hybrid rice, widely planted in Asia, is pathogen resistant and has superior yields, making it a major contributor to global food security. The two-line hybrid rice system, which utilizes mutants exhibiting photo-/thermo-sensitive genic male sterility (P/TGMS), is the leading hybrid rice breeding technology. Mutations in THERMO-SENSITIVE GENIC MALE STERILE 5 (TMS5) accounts for over 95% of current TGMS lines. We previously found that tms5 carries a mutation in ribonuclease ZS1. Despite its importance for breeding robust rice lines, the mechanism underlying tms5-mediated TGMS remains elusive. Here, we demonstrate that TMS5 is a tRNA 2′,3′-cyclic phosphatase. The tms5 mutation leads to accumulation of 2′,3′-cyclic phosphate (cP)-ΔCCA-tRNAs (tRNAs without 3′ CCA ended with cP), which is exacerbated by high temperatures, and reduction in the abundance of mature tRNAs, particularly alanine tRNAs (tRNA-Alas). Overexpression of tRNA-Alas in the tms5 mutant restores male fertility to 70%. Remarkably, male fertility of tms5 mutant is completely restored at high temperatures by knocking out OsVms1 which encodes the enzyme for cP-ΔCCA-tRNA generation. Our study reveals the mechanism underlying tms5-mediated TGMS in rice and provides mechanistic insight into the further improvement of TGMS in hybrid crop development.
{"title":"Impaired 2′,3′-cyclic phosphate tRNA repair causes thermo-sensitive genic male sterility in rice","authors":"Bin Yan, Chunyan Liu, Jing Sun, Yang Mao, Can Zhou, Ji Li, Wei Liu, Shengdong Li, Wei Yan, Chenjian Fu, Peng Qin, Xingxue Fu, Xinghui Zhao, Xianwei Song, Jiawei Nie, Feng Gao, Yuanzhu Yang, Yuhang Chen, Xiaofeng Cao","doi":"10.1038/s41422-024-01012-4","DOIUrl":"https://doi.org/10.1038/s41422-024-01012-4","url":null,"abstract":"<p>Hybrid rice, widely planted in Asia, is pathogen resistant and has superior yields, making it a major contributor to global food security. The two-line hybrid rice system, which utilizes mutants exhibiting photo-/thermo-sensitive genic male sterility (P/TGMS), is the leading hybrid rice breeding technology. Mutations in <i>THERMO-SENSITIVE GENIC MALE STERILE 5</i> (<i>TMS5</i>) accounts for over 95% of current TGMS lines. We previously found that <i>tms5</i> carries a mutation in ribonuclease Z<sup>S1</sup>. Despite its importance for breeding robust rice lines, the mechanism underlying <i>tms5</i>-mediated TGMS remains elusive. Here, we demonstrate that TMS5 is a tRNA 2′,3′-cyclic phosphatase. The <i>tms5</i> mutation leads to accumulation of 2′,3′-cyclic phosphate (cP)-ΔCCA-tRNAs (tRNAs without 3′ CCA ended with cP), which is exacerbated by high temperatures, and reduction in the abundance of mature tRNAs, particularly alanine tRNAs (tRNA-Alas). Overexpression of tRNA-Alas in the <i>tms5</i> mutant restores male fertility to 70%. Remarkably, male fertility of <i>tms5</i> mutant is completely restored at high temperatures by knocking out <i>OsVms1</i> which encodes the enzyme for cP-ΔCCA-tRNA generation. Our study reveals the mechanism underlying <i>tms5</i>-mediated TGMS in rice and provides mechanistic insight into the further improvement of TGMS in hybrid crop development.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s41422-024-01024-0
Ailong Song, Xudong Wu
{"title":"Mechanistic insights of substrate transport and inhibitor binding revealed by high-resolution structures of human norepinephrine transporter","authors":"Ailong Song, Xudong Wu","doi":"10.1038/s41422-024-01024-0","DOIUrl":"https://doi.org/10.1038/s41422-024-01024-0","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":44.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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