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

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}

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Author Correction: Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT3 receptors 作者更正：抗抑郁药物伏替西汀在人类和啮齿动物 5-HT3 受体上的活性结构决定因素。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-10 DOI: 10.1038/s41594-024-01346-y

Uriel López-Sánchez, Lachlan Jake Munro, Lucy Kate Ladefoged, Anders Juel Pedersen, Christian Colding Brun, Signe Meisner Lyngby, Delphine Baud, Céline Juillan-Binard, Miriam Grønlund Pedersen, Sarah C. R. Lummis, Benny Bang-Andersen, Birgit Schiøtt, Christophe Chipot, Guy Schoehn, Jacques Neyton, Francois Dehez, Hugues Nury, Anders S. Kristensen

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Chemical modifications, ions and water molecules in the sub-2 Å resolution structure of the human 80S ribosome 人类 80S 核糖体亚 2 Å 分辨率结构中的化学修饰、离子和水分子

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-06 DOI: 10.1038/s41594-024-01275-w

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The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA 分辨率为 1.9 Å 的人类 80S 核糖体结构揭示了 RNA 中化学修饰和离子的分子作用

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-06 DOI: 10.1038/s41594-024-01274-x

Samuel Holvec, Charles Barchet, Antony Lechner, Léo Fréchin, S. Nimali T. De Silva, Isabelle Hazemann, Philippe Wolff, Ottilie von Loeffelholz, Bruno P. Klaholz

{"title":"The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA","authors":"Samuel Holvec, Charles Barchet, Antony Lechner, Léo Fréchin, S. Nimali T. De Silva, Isabelle Hazemann, Philippe Wolff, Ottilie von Loeffelholz, Bruno P. Klaholz","doi":"10.1038/s41594-024-01274-x","DOIUrl":"10.1038/s41594-024-01274-x","url":null,"abstract":"The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. Here we present the 1.9 Å resolution cryo electron microscopy structure of the 80S human ribosome resolving numerous new ribosomal RNA modifications and functionally important ions such as Zn2+, K+ and Mg2+, including their associated individual water molecules. The 2′-O-methylation, pseudo-uridine and base modifications were confirmed by mass spectrometry, resulting in a complete investigation of the >230 sites, many of which could not be addressed previously. They choreograph key interactions within the RNA and at the interface with proteins, including at the ribosomal subunit interfaces of the fully assembled 80S ribosome. Uridine isomerization turns out to be a key mechanism for U–A base pair stabilization in RNA in general. The structural environment of chemical modifications and ions is primordial for the RNA architecture of the mature human ribosome, hence providing a structural framework to address their role in healthy states and in human diseases. The cryo-EM structure of the full 80S human ribosome is presented at 1.9 Å resolution. Numerous new chemical modifications are resolved, resulting in over 230 annotated sites cross-validated by mass spectometry. Ions and water molecules are seen to stabilize the RNA architecture.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264854","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

ATG16L1 induces the formation of phagophore-like membrane cups ATG16L1 可诱导形成类似吞噬细胞的膜杯

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-06-04 DOI: 10.1038/s41594-024-01300-y

Jagan Mohan, Satish B. Moparthi, Christine Girard-Blanc, Daniele Campisi, Stéphane Blanchard, Charlotte Nugues, Sowmya Rama, Audrey Salles, Esthel Pénard, Stéphane Vassilopoulos, Thomas Wollert

{"title":"ATG16L1 induces the formation of phagophore-like membrane cups","authors":"Jagan Mohan, Satish B. Moparthi, Christine Girard-Blanc, Daniele Campisi, Stéphane Blanchard, Charlotte Nugues, Sowmya Rama, Audrey Salles, Esthel Pénard, Stéphane Vassilopoulos, Thomas Wollert","doi":"10.1038/s41594-024-01300-y","DOIUrl":"10.1038/s41594-024-01300-y","url":null,"abstract":"The hallmark of non-selective autophagy is the formation of cup-shaped phagophores that capture bulk cytoplasm. The process is accompanied by the conjugation of LC3B to phagophores by an E3 ligase complex comprising ATG12–ATG5 and ATG16L1. Here we combined two complementary reconstitution approaches to reveal the function of LC3B and its ligase complex during phagophore expansion. We found that LC3B forms together with ATG12–ATG5–ATG16L1 a membrane coat that remodels flat membranes into cups that closely resemble phagophores. Mechanistically, we revealed that cup formation strictly depends on a close collaboration between LC3B and ATG16L1. Moreover, only LC3B, but no other member of the ATG8 protein family, promotes cup formation. ATG16L1 truncates that lacked the C-terminal membrane binding domain catalyzed LC3B lipidation but failed to assemble coats, did not promote cup formation and inhibited the biogenesis of non-selective autophagosomes. Our results thus demonstrate that ATG16L1 and LC3B induce and stabilize the characteristic cup-like shape of phagophores. Autophagy degrades cellular waste by engulfing it in phagophore membranes and delivering it to lysosomes for degradation. Here Mohan and colleagues identified a type of membrane coat that assembles on phagophores to guide their expansion.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246273","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

How Mcm10 converts the pre-replication complex into two diverging DNA forks Mcm10 如何将复制前复合物转化为两个不同的 DNA 叉

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-31 DOI: 10.1038/s41594-024-01333-3

引用次数: 0

Building up complexity in structural biology studies 提高结构生物学研究的复杂性

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-30 DOI: 10.1038/s41594-024-01324-4

Eva Nogales

引用次数: 0

A unifying model for membrane protein biogenesis 膜蛋白生物生成的统一模型

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-29 DOI: 10.1038/s41594-024-01296-5

Ramanujan S. Hegde, Robert J. Keenan

引用次数: 0

Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification Tead4 和 Tfap2c 在全能胚胎中产生双能性和双稳态开关，促进稳健的血统多样化

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-24 DOI: 10.1038/s41594-024-01311-9

Meng Zhu, Maciej Meglicki, Adiyant Lamba, Peizhe Wang, Christophe Royer, Karen Turner, Muhammad Abdullah Jauhar, Celine Jones, Tim Child, Kevin Coward, Jie Na, Magdalena Zernicka-Goetz

{"title":"Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification","authors":"Meng Zhu, Maciej Meglicki, Adiyant Lamba, Peizhe Wang, Christophe Royer, Karen Turner, Muhammad Abdullah Jauhar, Celine Jones, Tim Child, Kevin Coward, Jie Na, Magdalena Zernicka-Goetz","doi":"10.1038/s41594-024-01311-9","DOIUrl":"10.1038/s41594-024-01311-9","url":null,"abstract":"The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). The transcription factors TFAP2C and TEAD4 with activated RHOA accelerate embryo polarization. Here we show that these factors also accelerate the loss of totipotency. TFAP2C and TEAD4 paradoxically promote and inhibit Hippo signaling before lineage diversification: they drive expression of multiple Hippo regulators while also promoting apical domain formation, which inactivates Hippo. Each factor activates TE specifiers in bipotent cells, while TFAP2C also activates specifiers of the ICM fate. Asymmetric segregation of the apical domain reconciles the opposing regulation of Hippo signaling into Hippo OFF and the TE fate, or Hippo ON and the ICM fate. We propose that the bistable switch established by TFAP2C and TEAD4 is exploited to trigger robust lineage diversification in the developing embryo. Here the authors identify the transcription factors TFAP2C and TEAD4 as a bistable switch that reconciles into Hippo ON and OFF states, establishing a composite state at the eight-cell stage and critically regulating lineage diversification.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":null,"pages":null},"PeriodicalIF":16.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01311-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092133","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