Nature chemical biology最新文献

Chemoproteomic profiling reveals histone H4 dopaminylation inhibiting cell growth. 化学蛋白质组学分析显示组蛋白H4多巴胺化抑制细胞生长。

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-05-08 DOI: 10.1038/s41589-026-02225-x

Yinfeng Zhang, Yaqi Yang, Wenyan Wu, Min Zhang, Jianan Rao, Wenting Song, Yi Pan, Nan Shen, Linxue Li, Taishan Min, Kai Li, Xiaoqing Zhang, Xin-Yue Qiu, Shu-Yu Zhang, Wenjun Yang, Jianye Zang, Yu Liu, Xi Mo

{"title":"Chemoproteomic profiling reveals histone H4 dopaminylation inhibiting cell growth.","authors":"Yinfeng Zhang, Yaqi Yang, Wenyan Wu, Min Zhang, Jianan Rao, Wenting Song, Yi Pan, Nan Shen, Linxue Li, Taishan Min, Kai Li, Xiaoqing Zhang, Xin-Yue Qiu, Shu-Yu Zhang, Wenjun Yang, Jianye Zang, Yu Liu, Xi Mo","doi":"10.1038/s41589-026-02225-x","DOIUrl":"https://doi.org/10.1038/s41589-026-02225-x","url":null,"abstract":"Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine in proteins, represents a newly characterized class of posttranslational modifications. Because of the limited identification of substrates, the functions and molecular mechanisms associated with dopaminylation remain largely uncharacterized. Using an alkyne-functionalized dopamine probe, we developed a method for selectively enriching dopaminylated proteins in whole-cell systems. This approach provided a comprehensive resource of 4,133 dopamine-enriched protein candidates and peptide-level analysis with acid-cleavable tags identified 1,181 putative dopaminylated proteins, including histone H4 dopaminylation at Q27 (H4Q27dop), which we further validated. Functionally, H4Q27dop acts as a transcriptional repressor in a neuroblastoma model, where it blocks CEBPD binding at the CCND1 promoter, leading to transcriptional downregulation of CCND1 and subsequent suppression of cell proliferation. Our findings provide both a valuable resource of dopaminylated substrate proteins and a distinct mechanistic insight into how dopamine regulates neuroblastoma cell growth.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856633","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

Author Correction: Defining and refining the cysteine redoxome through sulfur chemical biology. 作者更正：通过硫化学生物学来定义和完善半胱氨酸氧化还原酶。

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-05-06 DOI: 10.1038/s41589-026-02239-5

Kate S Carroll, Jing Yang

引用次数: 0

Posttranslational modifications remodel proteome-wide ligandability. 翻译后修饰重塑了蛋白质组的配位性。

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-05-05 DOI: 10.1038/s41589-026-02216-y

Weichao Li, Qijia Wei, Manuel Llanos, Clara Gathmann, Paolo Governa, Tzu-Yuan Chiu, Jacob M Wozniak, Appaso M Jadhav, Matthew Holcomb, Jacob Cravatt, Ashok Dongre, Mia L Huang, Stefano Forli, Christopher G Parker

{"title":"Posttranslational modifications remodel proteome-wide ligandability.","authors":"Weichao Li, Qijia Wei, Manuel Llanos, Clara Gathmann, Paolo Governa, Tzu-Yuan Chiu, Jacob M Wozniak, Appaso M Jadhav, Matthew Holcomb, Jacob Cravatt, Ashok Dongre, Mia L Huang, Stefano Forli, Christopher G Parker","doi":"10.1038/s41589-026-02216-y","DOIUrl":"https://doi.org/10.1038/s41589-026-02216-y","url":null,"abstract":"Posttranslational modifications (PTMs) vastly expand the diversity of the human proteome, dynamically reshaping protein activity, interactions and localization in response to environmental, pharmacologic and disease-associated cues. However, their proteome-wide impact on small-molecule recognition-and, thus, druggability-remains largely unexplored. Here we present a chemical proteomic strategy to delineate how PTM states remodel protein ligandability in human cells. Using broad-spectrum photoaffinity probes, we identified more than 400 functionally diverse proteins whose ability to engage small molecules is impacted by phosphorylation or N-linked glycosylation status. Integrating binding site mapping with structural analyses reveals a diverse array of PTM-dependent pockets. Among these, we discovered that the phosphorylation status of common oncogenic KRAS mutants impacts the action of small molecules, including clinically approved inhibitors. These findings illuminate a previously underappreciated layer of proteome plasticity governed by PTMs and highlight opportunities to develop chemical probes that selectively target proteins in defined modification states.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840395","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

Author Correction: Development of the fluorescent probe CenSpark for labeling centrioles and cilia. 作者更正：用于标记中心粒和纤毛的荧光探针CenSpark的开发。

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-05-04 DOI: 10.1038/s41589-026-02236-8

Cédric Pourroy, Georgios N Hatzopoulos, Luc Reymond, Friso E Douma, Tatiana Favez, Marie Croisier, Sara Cascais, Caroline Arber, Benita Wolf, Daphne M Laan, Guillermina R Ramirez-San-Juan, François Kuonen, Saishree S Iyer, Ilya Grigoriev, Anna Akhmanova, Pierre Gönczy

引用次数: 0

Surveying hypocrealean fungi to identify biocontrol agents. 调查底厨真菌以确定生物防治剂。

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-04-28 DOI: 10.1038/s41589-026-02202-4

引用次数: 0

Regulatory elements on chromatin-associated RNA 15 years beyond RNA epigenetics. 染色质相关RNA的调控元件比RNA表观遗传学早了15年。

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-04-28 DOI: 10.1038/s41589-026-02207-z

Xiaoyang Dou,Chuan He

引用次数: 0

Resolving paclitaxel efficacy. 解决紫杉醇功效。

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-04-24 DOI: 10.1038/s41589-026-02208-y

Jawdat Al-Bassam, Aryan Taheri

引用次数: 0

Structural snapshots of self-splicing and circularization of the Anabaena precursor tRNA. 蓝藻前体tRNA的自剪接和环状结构快照。

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-04-24 DOI: 10.1038/s41589-026-02206-0

引用次数: 0

Condensation-independent intramodular translocation mechanism of the trans-AT polyketide synthase assembly line. 反式at聚酮合成酶装配线不依赖缩合的模内易位机制。

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-04-24 DOI: 10.1038/s41589-026-02209-x

Zhicheng Guo,Shijuan Wu,Xiaohua Wang,Gen Lu,Minghe Luo,Yulu Dong,Guo Sun,Zixin Deng,Guifa Zhai,Yuhui Sun

{"title":"Condensation-independent intramodular translocation mechanism of the trans-AT polyketide synthase assembly line.","authors":"Zhicheng Guo,Shijuan Wu,Xiaohua Wang,Gen Lu,Minghe Luo,Yulu Dong,Guo Sun,Zixin Deng,Guifa Zhai,Yuhui Sun","doi":"10.1038/s41589-026-02209-x","DOIUrl":"https://doi.org/10.1038/s41589-026-02209-x","url":null,"abstract":"Decarboxylative condensation drives chain elongation and translocation of polyketides and fatty acids. However, the mechanism by which nonelongating modules in trans-acyltransferase polyketide synthases (trans-AT PKSs) enable intramodular polyketide chain translocation without decarboxylation remains poorly understood. Here we elucidate a condensation-independent intramodular translocation mechanism in which KS0 within the nonelongating module operates as a transacylase, directly translocating the polyketide chain to its downstream cognate acyl carrier protein (ACP). Notably, the inherent demalonylation activity of trans-ATHtmA7 facilitates efficient ACP recycling ensuring intramodular translocation. Structural modeling and site-directed mutagenesis studies uncover a conserved KS0-ACP binding mode that underpins intramodular translocation across diverse nonelongating modules. Additionally, the strict discrimination of polyketide intermediate by the nonelongating module highlights its critical role in maintaining biosynthetic precision and efficiency. These findings provide mechanistic insights into evolutionary adaptation and sophisticated crosstalk between catalytic domains within trans-AT PKS, illuminating how metabolic flux and fidelity are maintained and opening avenues for polyketide engineering.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"54 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739090","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

Regulation for differential control 差动控制规则

IF 13.7 1区生物学

Nature chemical biology Pub Date : 2026-04-22 DOI: 10.1038/s41589-026-02203-3

Denise G. Hemmings, David N. Brindley

引用次数: 0