Nature chemical biology最新文献_第8页

One-carbon footprint in B cells B 细胞中的单碳足迹

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01703-4

Rebekah Steiner, Julia Jellusova

引用次数: 0

Persistent glucose consumption under antibiotic treatment protects bacterial community 抗生素治疗下的持续葡萄糖消耗保护细菌群落

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01708-z

Yuzhen Zhang, Yumin Cai, Xin Jin, Qile Wu, Fan Bai, Jintao Liu

{"title":"Persistent glucose consumption under antibiotic treatment protects bacterial community","authors":"Yuzhen Zhang, Yumin Cai, Xin Jin, Qile Wu, Fan Bai, Jintao Liu","doi":"10.1038/s41589-024-01708-z","DOIUrl":"https://doi.org/10.1038/s41589-024-01708-z","url":null,"abstract":"Antibiotics typically induce major physiological changes in bacteria. However, their effect on nutrient consumption remains unclear. Here we found that Escherichia coli communities can sustain normal levels of glucose consumption under a broad range of antibiotics. The community-living resulted in a low membrane potential in the bacteria, allowing slow antibiotic accumulation on treatment and better adaptation. Through multi-omics analysis, we identified a prevalent adaptive response characterized by the upregulation of lipid synthesis, which substantially contributes to sustained glucose consumption. The consumption was maintained by the periphery region of the community, thereby restricting glucose penetration into the community interior. The resulting spatial heterogeneity in glucose availability protected the interior from antibiotic accumulation in a membrane potential-dependent manner, ensuring rapid recovery of the community postantibiotic treatment. Our findings unveiled a community-level antibiotic response through spatial regulation of metabolism and suggested new strategies for antibiotic therapies.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974160","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

Single-cell sensor analyses reveal signaling programs enabling Ras-G12C drug resistance. 单细胞传感器分析揭示了促成 Ras-G12C 耐药性的信号传导程序。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-05 DOI: 10.1038/s41589-024-01684-4

Jason Z Zhang, Shao-En Ong, David Baker, Dustin J Maly

引用次数: 0

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2. 一种天然小分子通过靶向载脂蛋白 L2 缓解肝纤维化。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-05 DOI: 10.1038/s41589-024-01704-3

Lu Gan, Qiwei Jiang, Dong Huang, Xueji Wu, Xinying Zhu, Lei Wang, Wei Xie, Jialuo Huang, Runzhu Fan, Yihang Jing, Guihua Tang, Xiang David Li, Jianping Guo, Sheng Yin

{"title":"A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.","authors":"Lu Gan, Qiwei Jiang, Dong Huang, Xueji Wu, Xinying Zhu, Lei Wang, Wei Xie, Jialuo Huang, Runzhu Fan, Yihang Jing, Guihua Tang, Xiang David Li, Jianping Guo, Sheng Yin","doi":"10.1038/s41589-024-01704-3","DOIUrl":"10.1038/s41589-024-01704-3","url":null,"abstract":"Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-β1 (TGF-β1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893845","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

Nanometer-resolution tracking of single cargo reveals dynein motor mechanisms. 对单个货物的纳米分辨率追踪揭示了动力蛋白的运动机制。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-01 DOI: 10.1038/s41589-024-01694-2

Chunte Sam Peng, Yunxiang Zhang, Qian Liu, G Edward Marti, Yu-Wen Alvin Huang, Thomas C Südhof, Bianxiao Cui, Steven Chu

引用次数: 0

Photoproximity labeling of endogenous receptors in the live mouse brain in minutes. 在几分钟内对活体小鼠大脑中的内源性受体进行光接近标记。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-01 DOI: 10.1038/s41589-024-01692-4

Mikiko Takato, Seiji Sakamoto, Hiroshi Nonaka, Fátima Yuri Tanimura Valor, Tomonori Tamura, Itaru Hamachi

{"title":"Photoproximity labeling of endogenous receptors in the live mouse brain in minutes.","authors":"Mikiko Takato, Seiji Sakamoto, Hiroshi Nonaka, Fátima Yuri Tanimura Valor, Tomonori Tamura, Itaru Hamachi","doi":"10.1038/s41589-024-01692-4","DOIUrl":"https://doi.org/10.1038/s41589-024-01692-4","url":null,"abstract":"Understanding how protein-protein interaction networks in the brain give rise to cognitive functions necessitates their characterization in live animals. However, tools available for this purpose require potentially disruptive genetic modifications and lack the temporal resolution necessary to track rapid changes in vivo. Here we leverage affinity-based targeting and photocatalyzed singlet oxygen generation to identify neurotransmitter receptor-proximal proteins in the live mouse brain using only small-molecule reagents and minutes of photoirradiation. Our photooxidation-driven proximity labeling for proteome identification (named PhoxID) method not only recapitulated the known interactomes of three endogenous neurotransmitter receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), inhibitory γ-aminobutyric acid type A receptor and ionotropic glutamate receptor delta-2) but also uncovered age-dependent shifts, identifying NECTIN3 and IGSF3 as developmentally regulated AMPAR-proximal proteins in the cerebellum. Overall, this work establishes a flexible and generalizable platform to study receptor microenvironments in genetically intact specimens with an unprecedented temporal resolution.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875357","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

Balancing G protein selectivity and efficacy in the adenosine A2A receptor 平衡腺苷 A2A 受体中 G 蛋白的选择性和功效

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-07-31 DOI: 10.1038/s41589-024-01682-6

Louis-Philippe Picard, Alexander Orazietti, Duy Phuoc Tran, Andrejs Tucs, Sari Hagimoto, Zhenzhou Qi, Shuya Kate Huang, Koji Tsuda, Akio Kitao, Adnan Sljoka, R. Scott Prosser

{"title":"Balancing G protein selectivity and efficacy in the adenosine A2A receptor","authors":"Louis-Philippe Picard, Alexander Orazietti, Duy Phuoc Tran, Andrejs Tucs, Sari Hagimoto, Zhenzhou Qi, Shuya Kate Huang, Koji Tsuda, Akio Kitao, Adnan Sljoka, R. Scott Prosser","doi":"10.1038/s41589-024-01682-6","DOIUrl":"https://doi.org/10.1038/s41589-024-01682-6","url":null,"abstract":"The adenosine A2A receptor (A2AR) engages several G proteins, notably Go and its cognate Gs protein. This coupling promiscuity is facilitated by a dynamic ensemble, revealed by 19F nuclear magnetic resonance imaging of A2AR and G protein. Two transmembrane helix 6 (TM6) activation states, formerly associated with partial and full agonism, accommodate the differing volumes of Gs and Go. While nucleotide depletion biases TM7 toward a fully active state in A2AR–Gs, A2AR–Go is characterized by a dynamic inactive/intermediate fraction. Molecular dynamics simulations reveal that the NPxxY motif, a highly conserved switch, establishes a unique configuration in the A2AR–Go complex, failing to stabilize the helix-8 interface with Gs, and adoption of the active state. The resulting TM7 dynamics hamper G protein coupling, suggesting kinetic gating may be responsible for reduced efficacy in the noncognate G protein complex. Thus, dual TM6 activation states enable greater diversity of coupling partners while TM7 dynamics dictate coupling efficacy.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857822","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

Making use of machine learning 利用机器学习。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-07-30 DOI: 10.1038/s41589-024-01700-7

引用次数: 0

Solving the mystery of enediyne biosynthesis 解开烯二炔生物合成之谜

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-07-30 DOI: 10.1038/s41589-024-01686-2

Max B. Sosa, Michelle C. Y. Chang

引用次数: 0

Under pressure 在压力下

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-07-29 DOI: 10.1038/s41589-024-01696-0

Gene Chong

引用次数: 0