Nature chemical biology最新文献_第3页

Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors 用合成转录抑制因子直接抑制肿瘤缺氧反应

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-30 DOI: 10.1038/s41589-024-01716-z

Zeyu Qiao, Long C. Nguyen, Dongbo Yang, Christopher Dann, Deborah M. Thomas, Madeline Henn, Andrea Valdespino, Colin S. Swenson, Scott A. Oakes, Marsha Rich Rosner, Raymond E. Moellering

{"title":"Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors","authors":"Zeyu Qiao, Long C. Nguyen, Dongbo Yang, Christopher Dann, Deborah M. Thomas, Madeline Henn, Andrea Valdespino, Colin S. Swenson, Scott A. Oakes, Marsha Rich Rosner, Raymond E. Moellering","doi":"10.1038/s41589-024-01716-z","DOIUrl":"https://doi.org/10.1038/s41589-024-01716-z","url":null,"abstract":"Many oncogenic transcription factors (TFs) are considered to be undruggable because of their reliance on large protein–protein and protein–DNA interfaces. TFs such as hypoxia-inducible factors (HIFs) and X-box-binding protein 1 (XBP1) are induced by hypoxia and other stressors in solid tumors and bind to unfolded protein response element (UPRE) and hypoxia-induced response element (HRE) motifs to control oncogenic gene programs. Here, we report a strategy to create synthetic transcriptional repressors (STRs) that mimic the basic leucine zipper domain of XBP1 and recognize UPRE and HRE motifs. A lead molecule, STR22, binds UPRE and HRE DNA sequences with high fidelity and competes with both TFs in cells. Under hypoxia, STR22 globally suppresses HIF1α binding to HRE-containing promoters and enhancers, inhibits hypoxia-induced gene expression and blocks protumorigenic phenotypes in triple-negative breast cancer (TNBC) cells. In vivo, intratumoral and systemic STR22 treatment inhibited hypoxia-dependent gene expression, primary tumor growth and metastasis of TNBC tumors. These data validate a novel strategy to target the tumor hypoxia response through coordinated inhibition of TF–DNA binding.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101697","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

Genetic control over biogenic crystal morphogenesis in zebrafish 斑马鱼生物晶体形态发生的遗传控制

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-30 DOI: 10.1038/s41589-024-01722-1

Rachael Deis, Tali Lerer-Goldshtein, Olha Baiko, Zohar Eyal, Dolev Brenman-Begin, Moshe Goldsmith, Sylvia Kaufmann, Uwe Heinig, Yonghui Dong, Sofya Lushchekina, Neta Varsano, Tsviya Olender, Meital Kupervaser, Ziv Porat, Smadar Levin-Zaidman, Iddo Pinkas, Rita Mateus, Dvir Gur

{"title":"Genetic control over biogenic crystal morphogenesis in zebrafish","authors":"Rachael Deis, Tali Lerer-Goldshtein, Olha Baiko, Zohar Eyal, Dolev Brenman-Begin, Moshe Goldsmith, Sylvia Kaufmann, Uwe Heinig, Yonghui Dong, Sofya Lushchekina, Neta Varsano, Tsviya Olender, Meital Kupervaser, Ziv Porat, Smadar Levin-Zaidman, Iddo Pinkas, Rita Mateus, Dvir Gur","doi":"10.1038/s41589-024-01722-1","DOIUrl":"https://doi.org/10.1038/s41589-024-01722-1","url":null,"abstract":"Organisms evolve mechanisms that regulate the properties of biogenic crystals to support a wide range of functions, from vision and camouflage to communication and thermal regulation. Yet, the mechanism underlying the formation of diverse intracellular crystals remains enigmatic. Here we unravel the biochemical control over crystal morphogenesis in zebrafish iridophores. We show that the chemical composition of the crystals determines their shape, particularly through the ratio between the nucleobases guanine and hypoxanthine. We reveal that these variations in composition are genetically controlled through tissue-specific expression of specialized paralogs, which exhibit remarkable substrate selectivity. This orchestrated combination grants the organism with the capacity to generate a broad spectrum of crystal morphologies. Overall, our findings suggest a mechanism for the morphological and functional diversity of biogenic crystals and may, thus, inspire the development of genetically designed biomaterials and medical therapeutics.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101700","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

Coaching LSD1 to ignore acetylation 教导 LSD1 忽略乙酰化

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-28 DOI: 10.1038/s41589-024-01710-5

Joshua C. Black, Tatiana G. Kutateladze

引用次数: 0

Author Correction: Balancing G protein selectivity and efficacy in the adenosine A_2A receptor. 作者更正：平衡腺苷 A2A 受体中 G 蛋白的选择性和功效。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-28 DOI: 10.1038/s41589-024-01732-z

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

引用次数: 0

Massively parallel measurement of protein-protein interactions by sequencing using MP3-seq. 利用 MP3-seq 测序技术大规模并行测量蛋白质与蛋白质之间的相互作用。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-27 DOI: 10.1038/s41589-024-01718-x

Alexandr Baryshev, Alyssa La Fleur, Benjamin Groves, Cirstyn Michel, David Baker, Ajasja Ljubetič, Georg Seelig

引用次数: 0

Structural basis for intermodular communication in assembly-line polyketide biosynthesis 组装线多酮生物合成中模块间通信的结构基础

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-23 DOI: 10.1038/s41589-024-01709-y

Dillon P. Cogan, Alexander M. Soohoo, Muyuan Chen, Yan Liu, Krystal L. Brodsky, Chaitan Khosla

{"title":"Structural basis for intermodular communication in assembly-line polyketide biosynthesis","authors":"Dillon P. Cogan, Alexander M. Soohoo, Muyuan Chen, Yan Liu, Krystal L. Brodsky, Chaitan Khosla","doi":"10.1038/s41589-024-01709-y","DOIUrl":"https://doi.org/10.1038/s41589-024-01709-y","url":null,"abstract":"Assembly-line polyketide synthases (PKSs) are modular multi-enzyme systems with considerable potential for genetic reprogramming. Understanding how they selectively transport biosynthetic intermediates along a defined sequence of active sites could be harnessed to rationally alter PKS product structures. To investigate functional interactions between PKS catalytic and substrate acyl carrier protein (ACP) domains, we employed a bifunctional reagent to crosslink transient domain–domain interfaces of a prototypical assembly line, the 6-deoxyerythronolide B synthase, and resolved their structures by single-particle cryogenic electron microscopy (cryo-EM). Together with statistical per-particle image analysis of cryo-EM data, we uncovered interactions between ketosynthase (KS) and ACP domains that discriminate between intra-modular and inter-modular communication while reinforcing the relevance of conformational asymmetry during the catalytic cycle. Our findings provide a foundation for the structure-based design of hybrid PKSs comprising biosynthetic modules from different naturally occurring assembly lines.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042594","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

Degradable living plastics programmed by engineered spores 由工程孢子编程的可降解活塑料

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-21 DOI: 10.1038/s41589-024-01713-2

Chenwang Tang, Lin Wang, Jing Sun, Guangda Chen, Junfeng Shen, Liang Wang, Ying Han, Jiren Luo, Zhiying Li, Pei Zhang, Simin Zeng, Dianpeng Qi, Jin Geng, Ji Liu, Zhuojun Dai

{"title":"Degradable living plastics programmed by engineered spores","authors":"Chenwang Tang, Lin Wang, Jing Sun, Guangda Chen, Junfeng Shen, Liang Wang, Ying Han, Jiren Luo, Zhiying Li, Pei Zhang, Simin Zeng, Dianpeng Qi, Jin Geng, Ji Liu, Zhuojun Dai","doi":"10.1038/s41589-024-01713-2","DOIUrl":"https://doi.org/10.1038/s41589-024-01713-2","url":null,"abstract":"Plastics are widely used materials that pose an ecological challenge because their wastes are difficult to degrade. Embedding enzymes and biomachinery within polymers could enable the biodegradation and disposal of plastics. However, enzymes rarely function under conditions suitable for polymer processing. Here, we report degradable living plastics by harnessing synthetic biology and polymer engineering. We engineered Bacillus subtilis spores harboring the gene circuit for the xylose-inducible secretory expression of Burkholderia cepacia lipase (BC-lipase). The spores that were resilient to stresses during material processing were mixed with poly(caprolactone) to produce living plastics in various formats. Spore incorporation did not compromise the physical properties of the materials. Spore recovery was triggered by eroding the plastic surface, after which the BC-lipase released by the germinated cells caused near-complete depolymerization of the polymer matrix. This study showcases a method for fabricating green plastics that can function when the spores are latent and decay when the spores are activated and sheds light on the development of materials for sustainability.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013811","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

Polymers produced with depolymerase 用解聚酶生产的聚合物

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01723-0

Russell Johnson

引用次数: 0

Lipids on the move 移动中的脂质

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01725-y

Majda Bratovič

引用次数: 0

A pathway revisited 重新审视路径

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-20 DOI: 10.1038/s41589-024-01724-z

Gene Chong

引用次数: 0