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

Author Correction: Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase 作者更正：m3C RNA 甲基转移酶 METTL6 与 SerRS 丝氨酰-tRNA 合成酶复合体识别 tRNA 的结构基础。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-02-04 DOI: 10.1038/s41594-025-01508-6

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

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ELL3 regulates spindle assembly to prevent maternally inherited aneuploidy and infertility ELL3调节纺锤体组装以防止母体遗传的非整倍体和不孕症

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-22 DOI: 10.1038/s41594-024-01475-4

Bernhard Magerl, Tommaso Cavazza

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The structure and function of the ghrelin receptor coding for drug actions 编码药物作用的胃饥饿素受体的结构和功能

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-20 DOI: 10.1038/s41594-024-01481-6

Yuki Shiimura, Dohyun Im, Ryosuke Tany, Hidetsugu Asada, Ryoji Kise, Eon Kurumiya, Hideko Wakasugi-Masuho, Satoshi Yasuda, Kazuma Matsui, Jun-ichi Kishikawa, Takayuki Kato, Takeshi Murata, Masayasu Kojima, So Iwata, Ikuo Masuho

{"title":"The structure and function of the ghrelin receptor coding for drug actions","authors":"Yuki Shiimura, Dohyun Im, Ryosuke Tany, Hidetsugu Asada, Ryoji Kise, Eon Kurumiya, Hideko Wakasugi-Masuho, Satoshi Yasuda, Kazuma Matsui, Jun-ichi Kishikawa, Takayuki Kato, Takeshi Murata, Masayasu Kojima, So Iwata, Ikuo Masuho","doi":"10.1038/s41594-024-01481-6","DOIUrl":"10.1038/s41594-024-01481-6","url":null,"abstract":"Drugs targeting the ghrelin receptor hold therapeutic potential in anorexia, obesity and diabetes. However, developing effective drugs is challenging. To tackle this common issue across a broad drug target, this study aims to understand how anamorelin, the only approved drug targeting the ghrelin receptor, operates compared to other synthetic drugs. Our research elucidated the receptor’s structure with anamorelin and miniGq, unveiling anamorelin’s superagonistic activity. We demonstrated that ligands with distinct chemical structures uniquely bind to the receptor, resulting in diverse conformations and biasing signal transduction. Moreover, our study showcased the utility of structural information in effectively identifying natural genetic variations altering drug action and causing severe functional deficiencies, offering a basis for selecting the right medication on the basis of the individual’s genomic sequence. Thus, by building on structural analysis, this study enhances the foundational framework for selecting therapeutic agents targeting the ghrelin receptor, by effectively leveraging signaling bias and genetic variations. This study reveals how anamorelin, a superagonist targeting the ghrelin receptor, works compared to other drugs. Structural insights into ligand binding and genetic variations offer a framework for personalized therapies","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 3","pages":"531-542"},"PeriodicalIF":12.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989981","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

Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage 母体 ELL3 功能缺失导致卵母细胞非整倍体和早期流产

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-16 DOI: 10.1038/s41594-024-01471-8

Shiqi Zhu, Peng Xie, Yi Yang, Yan Wang, Chuanxin Zhang, Yu Zhang, Shuhan Si, Jin Zhang, Jingjing He, Hao Si, Ke Fang, Binbin Ma, Xu Jiang, Lindi Huang, Jiamin Li, Tian Min, Beihong Zheng, Lincui Da, Dianliang Lin, Kun Gao, Yuanyuan Li, Mingtao Huang, Fengchang Qiao, Haiqin Huo, Haoyang Feng, Han Zhao, Zijiang Chen, Zhengfeng Xu, Jing Xie, Hua Cao, Jin Liu, Xuebiao Yao, Wei Xie, Yan Sun, Keliang Wu, Bo Xiong, Ping Hu, Zhuojuan Luo, Chengqi Lin

{"title":"Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage","authors":"Shiqi Zhu, Peng Xie, Yi Yang, Yan Wang, Chuanxin Zhang, Yu Zhang, Shuhan Si, Jin Zhang, Jingjing He, Hao Si, Ke Fang, Binbin Ma, Xu Jiang, Lindi Huang, Jiamin Li, Tian Min, Beihong Zheng, Lincui Da, Dianliang Lin, Kun Gao, Yuanyuan Li, Mingtao Huang, Fengchang Qiao, Haiqin Huo, Haoyang Feng, Han Zhao, Zijiang Chen, Zhengfeng Xu, Jing Xie, Hua Cao, Jin Liu, Xuebiao Yao, Wei Xie, Yan Sun, Keliang Wu, Bo Xiong, Ping Hu, Zhuojuan Luo, Chengqi Lin","doi":"10.1038/s41594-024-01471-8","DOIUrl":"10.1038/s41594-024-01471-8","url":null,"abstract":"Up to an estimated 10% of women experience miscarriage in their lifetimes. Embryonic aneuploidy is a leading cause for miscarriage, infertility and congenital defects. Here we identify variants of ELL3, a gene encoding a transcription elongation factor, in couples who experienced consecutive early miscarriages due to embryonic aneuploidy. Maternal ELL3 knockout leads to mouse oocyte aneuploidy, subfertility and miscellaneous embryonic defects. Mechanistically, we find that ELL3 localizes to the spindle during meiosis, and that ELL3 depletion in both mouse and human oocytes increases the incidence of meiotic spindle abnormality. ELL3 coordinates with TPX2 to ensure the proper function of the microtubule motor KIF11. Live imaging analysis shows that ELL3 is paramount for promoting spindle assembly and driving chromosome movement. Together, our findings implicate maternal ELL3 deficiency in causing oocyte aneuploidy and early miscarriage. The authors show that ELL3 maintains chromosomal ploidy by promoting spindle assembly and driving chromosome movement in oocytes. Deficiency of ELL3 results in oocyte aneuploidy and may lead to early miscarriage.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 2","pages":"381-392"},"PeriodicalIF":12.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986739","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

Dynamic PRC1–CBX8 stabilizes a porous structure of chromatin condensates 动态PRC1-CBX8稳定了染色质凝聚物的多孔结构

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-15 DOI: 10.1038/s41594-024-01457-6

Michael Uckelmann, Vita Levina, Cyntia Taveneau, Xiao Han Ng, Varun Pandey, Jasmine Martinez, Shweta Mendiratta, Justin Houx, Marion Boudes, Hari Venugopal, Sylvain Trépout, Alex J. Fulcher, Qi Zhang, Sarena Flanigan, Minrui Li, Emma Sierecki, Yann Gambin, Partha Pratim Das, Oliver Bell, Alex de Marco, Chen Davidovich

{"title":"Dynamic PRC1–CBX8 stabilizes a porous structure of chromatin condensates","authors":"Michael Uckelmann, Vita Levina, Cyntia Taveneau, Xiao Han Ng, Varun Pandey, Jasmine Martinez, Shweta Mendiratta, Justin Houx, Marion Boudes, Hari Venugopal, Sylvain Trépout, Alex J. Fulcher, Qi Zhang, Sarena Flanigan, Minrui Li, Emma Sierecki, Yann Gambin, Partha Pratim Das, Oliver Bell, Alex de Marco, Chen Davidovich","doi":"10.1038/s41594-024-01457-6","DOIUrl":"10.1038/s41594-024-01457-6","url":null,"abstract":"The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin compacted by gene-repressing factors are unknown. Here, using cryo-electron tomography, we solved the three-dimensional structure of chromatin condensed by the polycomb repressive complex 1 (PRC1) in a complex with CBX8. PRC1-condensed chromatin is porous and stabilized through multivalent dynamic interactions of PRC1 with chromatin. Mechanistically, positively charged residues on the internally disordered regions of CBX8 mask negative charges on the DNA to stabilize the condensed state of chromatin. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure. In differentiated mouse embryonic stem cells, CBX8-bound chromatin remains accessible. These findings challenge the idea of rigidly compacted polycomb domains and instead provide a mechanistic framework for dynamic and accessible PRC1–chromatin condensates. Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility and low dynamics cause gene repression.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 3","pages":"520-530"},"PeriodicalIF":12.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01457-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981363","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

Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications 活性转录组蛋白翻译后修饰抑制PRC2的结构基础

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-07 DOI: 10.1038/s41594-024-01452-x

Trinity Cookis, Alexandria Lydecker, Paul Sauer, Vignesh Kasinath, Eva Nogales

{"title":"Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications","authors":"Trinity Cookis, Alexandria Lydecker, Paul Sauer, Vignesh Kasinath, Eva Nogales","doi":"10.1038/s41594-024-01452-x","DOIUrl":"10.1038/s41594-024-01452-x","url":null,"abstract":"Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms. Using cryo-electron microscopy, we reveal that histone H3 tails containing H3K36me3 engage poorly with PRC2 and preclude its effective interaction with chromatin, while H3K4me3 binds to the allosteric site in the EED subunit, acting as an antagonist that competes with activators required for spreading of the H3K27me3 repressive mark. Thus, the location of the H3K4me3 and H3K36me3 modifications along the H3 tail allows them to target two requirements for efficient trimethylation of H3K27 by PRC2. We further show that the JARID2 cofactor modulates PRC2 activity in the presence of these histone modifications. Structures reveal that histone H3K36me3 and H3K4me3 modifications reduce Polycomb repressive complex 2 (PRC2) function through the inhibition of histone tail engagement and antagonistic binding to the allosteric site, two important requirements for the efficient trimethylation of H3K27 by PRC2.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 2","pages":"393-404"},"PeriodicalIF":12.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01452-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934965","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

Intronic variant increases Parkinson disease risk by disrupting branchpoint sequence 内含子变异通过破坏分支点序列增加帕金森病风险

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-01-02 DOI: 10.1038/s41594-024-01424-1

引用次数: 0

Targeted degradation of membrane proteins 膜蛋白的靶向降解

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-12-31 DOI: 10.1038/s41594-024-01461-w

Grace Hohman, Michael Shahid, Mohamed Eldeeb

引用次数: 0

Insights into phosphate homeostasis regulation by XPR1 XPR1调控磷酸盐稳态的研究进展

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-12-30 DOI: 10.1038/s41594-024-01460-x

Daniel P. Bondeson

引用次数: 0

Transposon-triggered epigenetic chromatin dynamics modulate EFR-related pathogen response 转座子触发的表观遗传染色质动力学调节efr相关病原体反应

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-12-27 DOI: 10.1038/s41594-024-01440-1

Regina Mencia, Agustín L. Arce, Candela Houriet, Wenfei Xian, Adrián Contreras, Gautam Shirsekar, Detlef Weigel, Pablo A. Manavella

{"title":"Transposon-triggered epigenetic chromatin dynamics modulate EFR-related pathogen response","authors":"Regina Mencia, Agustín L. Arce, Candela Houriet, Wenfei Xian, Adrián Contreras, Gautam Shirsekar, Detlef Weigel, Pablo A. Manavella","doi":"10.1038/s41594-024-01440-1","DOIUrl":"10.1038/s41594-024-01440-1","url":null,"abstract":"Infectious diseases drive wild plant evolution and impact crop yield. Plants, like animals, sense biotic threats through pattern recognition receptors (PRRs). Overly robust immune responses can harm plants; thus, understanding the tuning of defense response mechanisms is crucial for developing pathogen-resistant crops. In this study, we found that an inverted-repeat transposon (EFR-associated IR, Ea-IR) located between the loci encoding PRRs ELONGATION FACTOR-TU RECEPTOR (EFR) and myosin XI-k (XI-k) in Arabidopsis affects chromatin organization, promoting the formation of a repressive chromatin loop. Upon pathogen infection, chromatin changes around EFR and XI-k correlate with increased EFR transcription. Pathogen-induced chromatin opening causes RNA polymerase II readthrough, producing a longer, Ea-IR-containing XI-k transcript, processed by Dicer-like enzymes into small RNAs, which reset chromatin to a repressive state attenuating the immune response after infection. Arabidopsis accessions lacking Ea-IR have higher basal EFR levels and resistance to pathogens. We show a scenario in which a transposon, chromatin organization and gene expression interact to fine-tune immune responses, during both the course of infection and the course of evolution. Here, the authors show that an inverted-repeat transposon located next to the pattern recognition receptor ELONGATION FACTOR-TU RECEPTOR (EFR)-encoding gene in Arabidopsis controls chromatin organization, EFR gene expression and plant immune response.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 1","pages":"199-211"},"PeriodicalIF":12.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01440-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887510","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