Nature chemical biology最新文献_第4页

Fucosylation of glycoproteins and glycolipids: opposing roles in cholera intoxication 糖蛋白和糖脂的岩藻糖基化：在霍乱中毒中的对立作用

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-16 DOI: 10.1038/s41589-024-01748-5

Atossa C. Ghorashi, Andrew Boucher, Stephanie A. Archer-Hartmann, Dani Zalem, Mehrnoush Taherzadeh Ghahfarrokhi, Nathan B. Murray, Rohit Sai Reddy Konada, Xunzhi Zhang, Chao Xing, Susann Teneberg, Parastoo Azadi, Ulf Yrlid, Jennifer J. Kohler

{"title":"Fucosylation of glycoproteins and glycolipids: opposing roles in cholera intoxication","authors":"Atossa C. Ghorashi, Andrew Boucher, Stephanie A. Archer-Hartmann, Dani Zalem, Mehrnoush Taherzadeh Ghahfarrokhi, Nathan B. Murray, Rohit Sai Reddy Konada, Xunzhi Zhang, Chao Xing, Susann Teneberg, Parastoo Azadi, Ulf Yrlid, Jennifer J. Kohler","doi":"10.1038/s41589-024-01748-5","DOIUrl":"https://doi.org/10.1038/s41589-024-01748-5","url":null,"abstract":"Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout (KO) of B3GNT5, which encodes an enzyme required for synthesis of lacto and neolacto series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. KO of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins and leads to increased CT binding and intoxication. KO of B3GNT5 in B3GALT5-KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into the molecular determinants regulating CT sensitivity of host cells.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440258","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

A broad anti-anti-CRISPR strategy 广泛的反CRISPR战略

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-15 DOI: 10.1038/s41589-024-01743-w

Yi Zhang, Yue Feng

引用次数: 0

ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway ML 增强的过氧化物酶体能力实现了多酶途径的区隔化

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-14 DOI: 10.1038/s41589-024-01759-2

Jordan J. Baker, Jie Shi, Shangying Wang, Elena M. Mujica, Simone Bianco, Sara Capponi, John E. Dueber

{"title":"ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway","authors":"Jordan J. Baker, Jie Shi, Shangying Wang, Elena M. Mujica, Simone Bianco, Sara Capponi, John E. Dueber","doi":"10.1038/s41589-024-01759-2","DOIUrl":"https://doi.org/10.1038/s41589-024-01759-2","url":null,"abstract":"Repurposing an organelle for specialized metabolism provides an avenue for fermentable, unicellular organisms such as Saccharomyces cerevisiae to mimic compartmentalization of metabolic pathways within different plant tissues. Peroxisomes are attractive organelles for repurposing as they are not required for yeast viability when grown on glucose and can efficiently compartmentalize heterologous enzymes to enable physical separation of cytosolic native metabolism and peroxisomal engineered metabolism. However, when not required, peroxisomes are repressed, leading to low functional capacities for heterologous proteins. Here we engineer peroxisomes with enhanced functional capacities, with the goal of compartmentalizing up to eight metabolic enzymes to enhance titers. We implement a machine learning pipeline that allows the identification of factors to overexpress, culminating in a 137% increase in peroxisome functional capacity compared to a wild-type strain. Improved pathway compartmentalization enables an 80% increase in the biosynthesis titers of the monoterpene geraniol, up to 9.5 g L−1.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"55 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430554","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

Sensitive fluorescent biosensor reveals differential subcellular regulation of PKC 灵敏的荧光生物传感器揭示了 PKC 的亚细胞调控差异

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-11 DOI: 10.1038/s41589-024-01758-3

Qi Su, Jing Zhang, Wei Lin, Jin-Fan Zhang, Alexandra C. Newton, Sohum Mehta, Jing Yang, Jin Zhang

{"title":"Sensitive fluorescent biosensor reveals differential subcellular regulation of PKC","authors":"Qi Su, Jing Zhang, Wei Lin, Jin-Fan Zhang, Alexandra C. Newton, Sohum Mehta, Jing Yang, Jin Zhang","doi":"10.1038/s41589-024-01758-3","DOIUrl":"https://doi.org/10.1038/s41589-024-01758-3","url":null,"abstract":"The protein kinase C (PKC) family of serine and threonine kinases, consisting of three distinctly regulated subfamilies, has been established as critical for various cellular functions. However, how PKC enzymes are regulated at different subcellular locations, particularly at emerging signaling hubs, is unclear. Here we present a sensitive excitation ratiometric C kinase activity reporter (ExRai-CKAR2) that enables the detection of minute changes (equivalent to 0.2% of maximum stimulation) in subcellular PKC activity. Using ExRai-CKAR2 with an enhanced diacylglycerol (DAG) biosensor, we uncover that G-protein-coupled receptor stimulation triggers sustained PKC activity at the endoplasmic reticulum and lysosomes, differentially mediated by Ca2+-sensitive conventional PKC and DAG-sensitive novel PKC, respectively. The high sensitivity of ExRai-CKAR2, targeted to either the cytosol or partitioning defective complexes, further enabled us to detect previously inaccessible endogenous atypical PKC activity in three-dimensional organoids. Taken together, ExRai-CKAR2 is a powerful tool for interrogating PKC regulation in response to physiological stimuli.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"15 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404935","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

Superoxide finds the niche 超氧化物找到利基

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-11 DOI: 10.1038/s41589-024-01742-x

Xuan Du, Jiamu Du

引用次数: 0

Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168 核糖体 H2A K13/15 单泛素化和 RNF168 邻近双重单泛素化的机制

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-10-11 DOI: 10.1038/s41589-024-01750-x

Huasong Ai, Zebin Tong, Zhiheng Deng, Qiang Shi, Shixian Tao, Gaoge Sun, Jiawei Liang, Maoshen Sun, Xiangwei Wu, Qingyun Zheng, Lujun Liang, Hang Yin, Jia-Bin Li, Shuai Gao, Changlin Tian, Lei Liu, Man Pan

{"title":"Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168","authors":"Huasong Ai, Zebin Tong, Zhiheng Deng, Qiang Shi, Shixian Tao, Gaoge Sun, Jiawei Liang, Maoshen Sun, Xiangwei Wu, Qingyun Zheng, Lujun Liang, Hang Yin, Jia-Bin Li, Shuai Gao, Changlin Tian, Lei Liu, Man Pan","doi":"10.1038/s41589-024-01750-x","DOIUrl":"https://doi.org/10.1038/s41589-024-01750-x","url":null,"abstract":"The DNA damage repair regulatory protein RNF168, a monomeric RING-type E3 ligase, has a crucial role in regulating cell fate and DNA repair by specific and efficient ubiquitination of the adjacent K13 and K15 (K13/15) sites at the H2A N-terminal tail. However, understanding how RNF168 coordinates with its cognate E2 enzyme UbcH5c to site-specifically ubiquitinate H2A K13/15 has long been hampered by the lack of high-resolution structures of RNF168 and UbcH5c~Ub (ubiquitin) in complex with nucleosomes. Here we developed chemical strategies and determined the cryo-electron microscopy structures of the RNF168–UbcH5c~Ub–nucleosome complex captured in transient H2A K13/15 monoubiquitination and adjacent dual monoubiquitination reactions, providing a ‘helix-anchoring’ mode for monomeric E3 ligase RNF168 on nucleosome in contrast to the ‘compass-binding’ mode of dimeric E3 ligases. Our work not only provides structural snapshots of H2A K13/15 site-specific monoubiquitination and adjacent dual monoubiquitination but also offers a near-atomic-resolution structural framework for understanding pathogenic amino acid substitutions and physiological modifications of RNF168.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"108 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404931","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

Chemical signaling in biofilm-mediated biofouling 生物膜介导的生物污损中的化学信号传递

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-09-30 DOI: 10.1038/s41589-024-01740-z

Xiaobo Liu, Ling Zou, Boqiao Li, Patrick Di Martino, Daniel Rittschof, Jin-Long Yang, James Maki, Weijie Liu, Ji-Dong Gu

{"title":"Chemical signaling in biofilm-mediated biofouling","authors":"Xiaobo Liu, Ling Zou, Boqiao Li, Patrick Di Martino, Daniel Rittschof, Jin-Long Yang, James Maki, Weijie Liu, Ji-Dong Gu","doi":"10.1038/s41589-024-01740-z","DOIUrl":"10.1038/s41589-024-01740-z","url":null,"abstract":"Biofouling is the undesirable accumulation of living organisms and their metabolites on submerged surfaces. Biofouling begins with adhesion of biomacromolecules and/or microorganisms and can lead to the subsequent formation of biofilms that are predominantly regulated by chemical signals, such as cyclic dinucleotides and quorum-sensing molecules. Biofilms typically release chemical cues that recruit or repel other invertebrate larvae and algal spores. As such, harnessing the biochemical mechanisms involved is a promising avenue for controlling biofouling. Here, we discuss how chemical signaling affects biofilm formation and dispersion in model species. We also examine how this translates to marine biofouling. Both inductive and inhibitory effects of chemical cues from biofilms on macrofouling are also discussed. Finally, we outline promising mitigation strategies by targeting chemical signaling to foster biofilm dispersion or inhibit biofouling. Biofouling causes a huge economic loss to our society. This Perspective examines the biofouling process from microfouling to macrofouling, discusses a spectrum of chemical signals that induce and inhibit biofouling and argues for potential management by targeting the signaling responsible for biofilm dispersion or biofouling inhibition.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1406-1419"},"PeriodicalIF":12.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329677","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

Unlocking the electrochemical functions of biomolecular condensates 开启生物分子凝聚物的电化学功能

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-09-26 DOI: 10.1038/s41589-024-01717-y

Yifan Dai, Zhen-Gang Wang, Richard N. Zare

{"title":"Unlocking the electrochemical functions of biomolecular condensates","authors":"Yifan Dai, Zhen-Gang Wang, Richard N. Zare","doi":"10.1038/s41589-024-01717-y","DOIUrl":"10.1038/s41589-024-01717-y","url":null,"abstract":"Biomolecular condensation is a key mechanism for organizing cellular processes in a spatiotemporal manner. The phase-transition nature of this process defines a density transition of the whole solution system. However, the physicochemical features and the electrochemical functions brought about by condensate formation are largely unexplored. We here illustrate the fundamental principles of how the formation of condensates generates distinct electrochemical features in the dilute phase, the dense phase and the interfacial region. We discuss the principles by which these distinct chemical and electrochemical environments can modulate biomolecular functions through the effects brought about by water, ions and electric fields. We delineate the potential impacts on cellular behaviors due to the modulation of chemical and electrochemical environments through condensate formation. This Perspective is intended to serve as a general road map to conceptualize condensates as electrochemically active entities and to assess their functions from a physical chemistry aspect. This Perspective discusses how macromolecular condensation can regulate the electrochemistry to affect biological function in living cells and provides a framework to study the electrochemical functions of biomolecular condensates.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1420-1433"},"PeriodicalIF":12.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321403","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

Direct mapping of tyrosine sulfation states in native peptides by nanopore 利用纳米孔直接绘制原生肽中的酪氨酸硫酸化状态图

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-09-25 DOI: 10.1038/s41589-024-01734-x

Hongyan Niu, Meng-Yin Li, Yan Gao, Jun-Ge Li, Jie Jiang, Yi-Lun Ying, Yi-Tao Long

{"title":"Direct mapping of tyrosine sulfation states in native peptides by nanopore","authors":"Hongyan Niu, Meng-Yin Li, Yan Gao, Jun-Ge Li, Jie Jiang, Yi-Lun Ying, Yi-Tao Long","doi":"10.1038/s41589-024-01734-x","DOIUrl":"https://doi.org/10.1038/s41589-024-01734-x","url":null,"abstract":"Sulfation is considered the most prevalent post-translational modification (PTM) on tyrosine; however, its importance is frequently undervalued due to difficulties in direct and unambiguous determination from phosphorylation. Here we present a sequence-independent strategy to directly map and quantify the tyrosine sulfation states in universal native peptides using an engineered protein nanopore. Molecular dynamics simulations and nanopore mutations reveal specific interactions between tyrosine sulfation and the engineered nanopore, dominating identification across diverse peptide sequences. We show a nanopore framework to discover tyrosine sulfation in unknown peptide fragments digested from a native protein and determine the sequence of the sulfated fragment based on current blockade enhancement induced by sulfation. Moreover, our method allows direct observation of peptide sulfation in ultra-low abundance, down to 1%, and distinguishes it from isobaric phosphorylation. This sequence-independent strategy suggests the potential of nanopore to explore specific PTMs in real-life samples and at the omics level.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"11 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317259","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

Partitioning of a 2-bit hash function across 66 communicating cells 在 66 个通信单元中划分 2 位散列函数

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-09-24 DOI: 10.1038/s41589-024-01730-1

Jai P. Padmakumar, Jessica J. Sun, William Cho, Yangruirui Zhou, Christopher Krenz, Woo Zhong Han, Douglas Densmore, Eduardo D. Sontag, Christopher A. Voigt

引用次数: 0