Nature Structural & Molecular Biology最新文献_第2页

AlphaFold3 takes a step toward decoding molecular behavior and biological computation AlphaFold3 向解码分子行为和生物计算迈出了一步

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-08 DOI: 10.1038/s41594-024-01350-2

Rohit Roy, Hashim M. Al-Hashimi

引用次数: 0

Obscure DNA sequences unveil a new cancer target 晦涩难懂的 DNA 序列揭示了新的癌症靶点

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-08 DOI: 10.1038/s41594-024-01347-x

Agnel Sfeir

引用次数: 0

Cryo-EM structures of γ-TuRC reveal molecular insights into microtubule nucleation γ-TuRC的低温电子显微镜结构揭示了微管成核的分子奥秘

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-07-02 DOI: 10.1038/s41594-024-01345-z

Léa Mammri, Paul T. Conduit

引用次数: 0

Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase m3C RNA 甲基转移酶 METTL6 与 SerRS 丝氨酰-tRNA 合成酶复合物识别 tRNA 的结构基础

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-25 DOI: 10.1038/s41594-024-01341-3

Philipp Throll, Luciano G. Dolce, Palma Rico-Lastres, Katharina Arnold, Laura Tengo, Shibom Basu, Stefanie Kaiser, Robert Schneider, Eva Kowalinski

{"title":"Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase","authors":"Philipp Throll, Luciano G. Dolce, Palma Rico-Lastres, Katharina Arnold, Laura Tengo, Shibom Basu, Stefanie Kaiser, Robert Schneider, Eva Kowalinski","doi":"10.1038/s41594-024-01341-3","DOIUrl":"10.1038/s41594-024-01341-3","url":null,"abstract":"Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (m3C) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human m3C tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNASer. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNASer substrate selection factor for METTL6. We demonstrate that SerRS augments the methylation activity of METTL6 and that direct contacts between METTL6 and SerRS are necessary for efficient tRNASer methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNASer, we postulate a universal tRNA-binding mode for m3C RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors. The authors use cryo-electron microscopy and biochemistry to reveal how 3-methylcytosine (m3C) methyltransferases bind tRNA. They also find that the human m3C methyltransferase METTL6 forms a tRNA-dependent complex with seryl-tRNA synthetase to methylate target tRNAs efficiently.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01341-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The tRNA methyltransferase METTL6 requires seryl-tRNA synthetase for tRNASer targeting tRNA甲基转移酶METTL6需要丝氨酰-tRNA合成酶来实现tRNASer靶向作用

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-25 DOI: 10.1038/s41594-024-01343-1

引用次数: 0

Structure of the poxvirus core 痘病毒核心的结构

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-18 DOI: 10.1038/s41594-024-01331-5

Fasséli Coulibaly

引用次数: 0

Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms 多种状态下 Smc5/6 的冷冻电镜结构揭示了其组装和功能机制

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-18 DOI: 10.1038/s41594-024-01319-1

Qian Li, Jun Zhang, Cory Haluska, Xiang Zhang, Lei Wang, Guangfeng Liu, Zhaoning Wang, Duo Jin, Tong Cheng, Hongxia Wang, Yuan Tian, Xiangxi Wang, Lei Sun, Xiaolan Zhao, Zhenguo Chen, Lanfeng Wang

{"title":"Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms","authors":"Qian Li, Jun Zhang, Cory Haluska, Xiang Zhang, Lei Wang, Guangfeng Liu, Zhaoning Wang, Duo Jin, Tong Cheng, Hongxia Wang, Yuan Tian, Xiangxi Wang, Lei Sun, Xiaolan Zhao, Zhenguo Chen, Lanfeng Wang","doi":"10.1038/s41594-024-01319-1","DOIUrl":"10.1038/s41594-024-01319-1","url":null,"abstract":"Smc5/6 is a member of the eukaryotic structural maintenance of chromosomes (SMC) family of complexes with important roles in genome maintenance and viral restriction. However, limited structural understanding of Smc5/6 hinders the elucidation of its diverse functions. Here, we report cryo-EM structures of the budding yeast Smc5/6 complex in eight-subunit, six-subunit and five-subunit states. Structural maps throughout the entire length of these complexes reveal modularity and key elements in complex assembly. We show that the non-SMC element (Nse)2 subunit supports the overall shape of the complex and uses a wedge motif to aid the stability and function of the complex. The Nse6 subunit features a flexible hook region for attachment to the Smc5 and Smc6 arm regions, contributing to the DNA repair roles of the complex. Our results also suggest a structural basis for the opposite effects of the Nse1–3–4 and Nse5–6 subcomplexes in regulating Smc5/6 ATPase activity. Collectively, our integrated structural and functional data provide a framework for understanding Smc5/6 assembly and function. Cryo-EM structures covering full-length yeast Smc5/6 in three states and the accompanying mutagenesis data reveal multiple new structural and functional features of this unique SMC complex.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334155","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}

引用次数: 0

Structural basis for the dynamic chaperoning of disordered clients by Hsp90 Hsp90 对无序客户进行动态陪衬的结构基础

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-18 DOI: 10.1038/s41594-024-01337-z

Xiaozhan Qu, Shuo Zhao, Chanjuan Wan, Lei Zhu, Tuo Ji, Paolo Rossi, Junfeng Wang, Charalampos G. Kalodimos, Chao Wang, Weiya Xu, Chengdong Huang

{"title":"Structural basis for the dynamic chaperoning of disordered clients by Hsp90","authors":"Xiaozhan Qu, Shuo Zhao, Chanjuan Wan, Lei Zhu, Tuo Ji, Paolo Rossi, Junfeng Wang, Charalampos G. Kalodimos, Chao Wang, Weiya Xu, Chengdong Huang","doi":"10.1038/s41594-024-01337-z","DOIUrl":"10.1038/s41594-024-01337-z","url":null,"abstract":"Molecular chaperone heat shock protein 90 (Hsp90) is a ubiquitous regulator that fine-tunes and remodels diverse client proteins, exerting profound effects on normal biology and diseases. Unraveling the mechanistic details of Hsp90’s function requires atomic-level insights into its client interactions throughout the adenosine triphosphate-coupled functional cycle. However, the structural details of the initial encounter complex in the chaperone cycle, wherein Hsp90 adopts an open conformation while engaging with the client, remain elusive. Here, using nuclear magnetic resonance spectroscopy, we determined the solution structure of Hsp90 in its open state, bound to a disordered client. Our findings reveal that Hsp90 uses two distinct binding sites, collaborating synergistically to capture discrete hydrophobic segments within client proteins. This bipartite interaction generates a versatile complex that facilitates rapid conformational sampling. Moreover, our investigations spanning various clients and Hsp90 orthologs demonstrate a pervasive mechanism used by Hsp90 orthologs to accommodate the vast array of client proteins. Collectively, our work contributes to establish a unified conceptual and mechanistic framework, elucidating the intricate interplay between Hsp90 and its clients. Here, using nuclear magnetic resonance spectroscopy, the authors delineate how the molecular chaperone Hsp90, in its open state, uses its two middle domains to synergistically capture a disordered client in a highly dynamic manner, forming a bipartite complex.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334417","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}

引用次数: 0

Efficient selenium use by PRDX6 suppresses iron toxicity and ferroptosis PRDX6 对硒的高效利用可抑制铁毒性和铁变态反应

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-12 DOI: 10.1038/s41594-024-01330-6

引用次数: 0

PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis PRDX6 可提高硒的利用率，限制铁中毒和铁变态反应

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-12 DOI: 10.1038/s41594-024-01329-z

Hiroaki Fujita, Yu-ki Tanaka, Seiryo Ogata, Noriyuki Suzuki, Sota Kuno, Uladzimir Barayeu, Takaaki Akaike, Yasumitsu Ogra, Kazuhiro Iwai

{"title":"PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis","authors":"Hiroaki Fujita, Yu-ki Tanaka, Seiryo Ogata, Noriyuki Suzuki, Sota Kuno, Uladzimir Barayeu, Takaaki Akaike, Yasumitsu Ogra, Kazuhiro Iwai","doi":"10.1038/s41594-024-01329-z","DOIUrl":"10.1038/s41594-024-01329-z","url":null,"abstract":"Ferroptosis is a form of regulated cell death induced by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides via a catalytic selenocysteine (Sec) residue. Sec, the genetically encoded 21st amino acid, is biosynthesized from a reactive selenium donor on its cognate tRNA[Ser]Sec. It is thought that intracellular selenium must be delivered ‘safely’ and ‘efficiently’ by a carrier protein owing to its high reactivity and very low concentrations. Here, we identified peroxiredoxin 6 (PRDX6) as a novel selenoprotein synthesis factor. Loss of PRDX6 decreases the expression of selenoproteins and induces ferroptosis via a reduction in GPX4. Mechanistically, PRDX6 increases the efficiency of intracellular selenium utilization by transferring selenium between proteins within the selenocysteyl-tRNA[Ser]Sec synthesis machinery, leading to efficient synthesis of selenocysteyl-tRNA[Ser]Sec. These findings highlight previously unidentified selenium metabolic systems and provide new insights into ferroptosis. The authors identified PRDX6 as a novel selenoprotein synthesis factor performing an iron-induced ferroptosis screen. They reveal that PRDX6 greatly facilitates selenium utilization for selenoprotein synthesis by acting as a selenide carrier protein.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01329-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0