Resolving protein–protein interactions (PPIs) inside biomolecular condensates is crucial for elucidating their functions and regulation mechanisms. The transient nature of condensates and the multiple localizations of clients, however, have rendered it challenging to determine compartment-specific PPIs. Here we developed a condensation-enhanced, spatially directed, metabolic incorporation-assisted photocrosslinking strategy—termed DenseMAP—for spatiotemporally resolved dissection of the direct protein interactome within condensates. By leveraging our condensation-enhanced photocrosslinker and the spatially directed biotin tagging, DenseMAP enabled stress-granule-specific interactome mapping of the N6-methyladenosine readers YTHDF1 and YTHDF2, and uncovered the functional role of phosphorylation on the SARS-CoV-2 nucleocapsid protein in regulating virus replication. Further applying DenseMAP for direct interactome mapping of the subcompartmental scaffold protein NPM1 deciphered nucleolar granular component proteome, and unveiled the critical role of SUMOylation in controlling nucleolar proteome homeostasis. DenseMAP provides a platform technology for analysing functional PPI networks within subcellular and subcompartmental condensates under diverse physiological and/or pathological settings. Now a generalizable method that couples spatially directed tagging with condensation-enhanced crosslinking—termed DenseMAP—has been developed for profiling the spatiotemporal protein interactome within biomolecular condensates. By linking the information between protein interactions and subcellular locations, DenseMAP has uncovered regulatory mechanisms in subcellular and subcompartmental condensates.
{"title":"Spatiotemporal protein interactome profiling through condensation-enhanced photocrosslinking","authors":"Kexin Li, Xiao Xie, Rui Gao, Zhaoming Chen, Mingdong Yang, Zhihui Wen, Yicheng Weng, Xinyuan Fan, Gong Zhang, Lu Liu, Xiangmei Zeng, Yu Han, Mengrui Cao, Xin Wang, Jiaofeng Li, Zhenlin Yang, Tingting Li, Peng R. Chen","doi":"10.1038/s41557-024-01663-1","DOIUrl":"10.1038/s41557-024-01663-1","url":null,"abstract":"Resolving protein–protein interactions (PPIs) inside biomolecular condensates is crucial for elucidating their functions and regulation mechanisms. The transient nature of condensates and the multiple localizations of clients, however, have rendered it challenging to determine compartment-specific PPIs. Here we developed a condensation-enhanced, spatially directed, metabolic incorporation-assisted photocrosslinking strategy—termed DenseMAP—for spatiotemporally resolved dissection of the direct protein interactome within condensates. By leveraging our condensation-enhanced photocrosslinker and the spatially directed biotin tagging, DenseMAP enabled stress-granule-specific interactome mapping of the N6-methyladenosine readers YTHDF1 and YTHDF2, and uncovered the functional role of phosphorylation on the SARS-CoV-2 nucleocapsid protein in regulating virus replication. Further applying DenseMAP for direct interactome mapping of the subcompartmental scaffold protein NPM1 deciphered nucleolar granular component proteome, and unveiled the critical role of SUMOylation in controlling nucleolar proteome homeostasis. DenseMAP provides a platform technology for analysing functional PPI networks within subcellular and subcompartmental condensates under diverse physiological and/or pathological settings. Now a generalizable method that couples spatially directed tagging with condensation-enhanced crosslinking—termed DenseMAP—has been developed for profiling the spatiotemporal protein interactome within biomolecular condensates. By linking the information between protein interactions and subcellular locations, DenseMAP has uncovered regulatory mechanisms in subcellular and subcompartmental condensates.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 1","pages":"111-123"},"PeriodicalIF":19.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ubiquitin is a chemist’s playground","authors":"Jakob Farnung, Brenda A. Schulman","doi":"10.1038/s41557-024-01660-4","DOIUrl":"10.1038/s41557-024-01660-4","url":null,"abstract":"Jakob Farnung and Brenda Schulman detail chemical diversification that endows the protein ubiquitin with many important cellular functions.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1918-1918"},"PeriodicalIF":19.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1038/s41557-024-01666-y
Christy J. Cho, Taeyang An, Yei-Chen Lai, Alberto Vázquez-Salazar, Alessandro Fracassi, Roberto J. Brea, Irene A. Chen, Neal K. Devaraj
All known forms of life are composed of cells, whose boundaries are defined by lipid membranes that separate and protect cell contents from the environment. It is unknown how the earliest forms of life were compartmentalized. Several models have suggested a role for single-chain lipids such as fatty acids, but the membranes formed are often unstable, particularly when made from shorter alkyl chains (≤C8) that were probably more prevalent on prebiotic Earth. Here we show that the amino acid cysteine can spontaneously react with two short-chain (C8) thioesters to form diacyl lipids, generating protocell-like membrane vesicles. The three-component reaction takes place rapidly in water using low concentrations of reactants. Silica can catalyse the formation of protocells through a simple electrostatic mechanism. Several simple aminothiols react to form diacyl lipids, including short peptides. The protocells formed are compatible with functional ribozymes, suggesting that coupling of multiple short-chain precursors may have provided membrane building blocks during the early evolution of cells. It is unknown what lipids formed the membranes of early life forms. Now it has been shown that protocell vesicles can assemble from diacylcysteines, which form spontaneously from cysteine and short-chain thioesters. Silica catalyses membrane formation, and protocells formed from diacylcysteine lipids are compatible with ribozyme activity.
{"title":"Protocells by spontaneous reaction of cysteine with short-chain thioesters","authors":"Christy J. Cho, Taeyang An, Yei-Chen Lai, Alberto Vázquez-Salazar, Alessandro Fracassi, Roberto J. Brea, Irene A. Chen, Neal K. Devaraj","doi":"10.1038/s41557-024-01666-y","DOIUrl":"10.1038/s41557-024-01666-y","url":null,"abstract":"All known forms of life are composed of cells, whose boundaries are defined by lipid membranes that separate and protect cell contents from the environment. It is unknown how the earliest forms of life were compartmentalized. Several models have suggested a role for single-chain lipids such as fatty acids, but the membranes formed are often unstable, particularly when made from shorter alkyl chains (≤C8) that were probably more prevalent on prebiotic Earth. Here we show that the amino acid cysteine can spontaneously react with two short-chain (C8) thioesters to form diacyl lipids, generating protocell-like membrane vesicles. The three-component reaction takes place rapidly in water using low concentrations of reactants. Silica can catalyse the formation of protocells through a simple electrostatic mechanism. Several simple aminothiols react to form diacyl lipids, including short peptides. The protocells formed are compatible with functional ribozymes, suggesting that coupling of multiple short-chain precursors may have provided membrane building blocks during the early evolution of cells. It is unknown what lipids formed the membranes of early life forms. Now it has been shown that protocell vesicles can assemble from diacylcysteines, which form spontaneously from cysteine and short-chain thioesters. Silica catalyses membrane formation, and protocells formed from diacylcysteine lipids are compatible with ribozyme activity.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 1","pages":"148-155"},"PeriodicalIF":19.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1038/s41557-024-01662-2
Md Azimul Haque, Andrew Grieder, Steven P. Harvey, Roman Brunecky, Jiselle Y. Ye, Bennett Addison, Junxiang Zhang, Yifan Dong, Yi Xie, Matthew P. Hautzinger, Heshan Hewa Walpitage, Kai Zhu, Jeffrey L. Blackburn, Zeev Valy Vardeny, David B. Mitzi, Joseph J. Berry, Seth R. Marder, Yuan Ping, Matthew C. Beard, Joseph M. Luther
In hybrid metal halide perovskites, chiroptical properties typically arise from structural symmetry breaking by incorporating a chiral A-site organic cation within the structure, which may limit the compositional space. Here we demonstrate highly efficient remote chirality transfer where chirality is imposed on an otherwise achiral hybrid metal halide semiconductor by a proximal chiral molecule that is not interspersed as part of the structure yet leads to large circular dichroism dissymmetry factors (gCD) of up to 10−2. Density functional theory calculations reveal that the transfer of stereochemical information from the chiral proximal molecule to the inorganic framework is mediated by selective interaction with divalent metal cations. Anchoring of the chiral molecule induces a centro-asymmetric distortion, which is discernible up to four inorganic layers into the metal halide lattice. This concept is broadly applicable to low-dimensional hybrid metal halides with various dimensionalities (1D and 2D) allowing independent control of the composition and degree of chirality. Hybrid metal halide semiconductors typically rely on chiral A-site ammonium cations for chiral induction in the lattice. Now it has been shown that chirality in low-dimensional achiral metal halide semiconductors can be induced by non-ammonium, non-A-site chiral molecules through remote stereocontrol of the inorganic framework.
在混合金属卤化物包光体中，手性特性通常来自于结构对称性的破坏，即在结构上加入手性 A 位有机阳离子，这可能会限制组成空间。在这里，我们展示了高效的远程手性转移，即通过近端手性分子将手性强加给原本非手性的混合卤化金属半导体，该分子并不作为结构的一部分穿插其中，但却能产生高达 10-2 的大圆二色性不对称因子 (gCD)。密度泛函理论计算显示，立体化学信息从手性近端分子到无机框架的传递是通过与二价金属阳离子的选择性相互作用进行的。手性分子的锚定会引起中心不对称变形，这种变形在金属卤化物晶格的四个无机层中都可以看到。这一概念广泛适用于具有不同维度（一维和二维）的低维混合金属卤化物，可独立控制手性的组成和程度。
{"title":"Remote chirality transfer in low-dimensional hybrid metal halide semiconductors","authors":"Md Azimul Haque, Andrew Grieder, Steven P. Harvey, Roman Brunecky, Jiselle Y. Ye, Bennett Addison, Junxiang Zhang, Yifan Dong, Yi Xie, Matthew P. Hautzinger, Heshan Hewa Walpitage, Kai Zhu, Jeffrey L. Blackburn, Zeev Valy Vardeny, David B. Mitzi, Joseph J. Berry, Seth R. Marder, Yuan Ping, Matthew C. Beard, Joseph M. Luther","doi":"10.1038/s41557-024-01662-2","DOIUrl":"10.1038/s41557-024-01662-2","url":null,"abstract":"In hybrid metal halide perovskites, chiroptical properties typically arise from structural symmetry breaking by incorporating a chiral A-site organic cation within the structure, which may limit the compositional space. Here we demonstrate highly efficient remote chirality transfer where chirality is imposed on an otherwise achiral hybrid metal halide semiconductor by a proximal chiral molecule that is not interspersed as part of the structure yet leads to large circular dichroism dissymmetry factors (gCD) of up to 10−2. Density functional theory calculations reveal that the transfer of stereochemical information from the chiral proximal molecule to the inorganic framework is mediated by selective interaction with divalent metal cations. Anchoring of the chiral molecule induces a centro-asymmetric distortion, which is discernible up to four inorganic layers into the metal halide lattice. This concept is broadly applicable to low-dimensional hybrid metal halides with various dimensionalities (1D and 2D) allowing independent control of the composition and degree of chirality. Hybrid metal halide semiconductors typically rely on chiral A-site ammonium cations for chiral induction in the lattice. Now it has been shown that chirality in low-dimensional achiral metal halide semiconductors can be induced by non-ammonium, non-A-site chiral molecules through remote stereocontrol of the inorganic framework.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 1","pages":"29-37"},"PeriodicalIF":19.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1038/s41557-024-01661-3
Adsorbents for efficient hydrogen storage require both a high gravimetric and volumetric storage capacity. A catenation strategy guided by hydrogen bonding is now demonstrated for the construction of supramolecular crystals with both high volumetric and large gravimetric surface areas, robustness and ideal pore diameters, which contribute to their good performance for hydrogen storage.
{"title":"Supramolecular crystals for hydrogen storage","authors":"","doi":"10.1038/s41557-024-01661-3","DOIUrl":"10.1038/s41557-024-01661-3","url":null,"abstract":"Adsorbents for efficient hydrogen storage require both a high gravimetric and volumetric storage capacity. A catenation strategy guided by hydrogen bonding is now demonstrated for the construction of supramolecular crystals with both high volumetric and large gravimetric surface areas, robustness and ideal pore diameters, which contribute to their good performance for hydrogen storage.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 12","pages":"1941-1942"},"PeriodicalIF":19.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1038/s41557-024-01657-z
Bruce C. Gibb
About two thirds of western society are extroverts, but the contemplative nature of science means that this is not true of the academic population. Bruce Gibb discusses extraversion and introversion in science and asks whether the movement towards larger projects involving teams of scientists is making it harder for introverts and for disruptive discoveries.
{"title":"The chemical sciences need introverts too","authors":"Bruce C. Gibb","doi":"10.1038/s41557-024-01657-z","DOIUrl":"10.1038/s41557-024-01657-z","url":null,"abstract":"About two thirds of western society are extroverts, but the contemplative nature of science means that this is not true of the academic population. Bruce Gibb discusses extraversion and introversion in science and asks whether the movement towards larger projects involving teams of scientists is making it harder for introverts and for disruptive discoveries.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1737-1738"},"PeriodicalIF":19.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1038/s41557-024-01659-x
Khalyd J. Clay, Ryan A. Shenvi
Much natural-product-based drug discovery has depended on the practices of Indigenous Peoples, who have sometimes invested centuries of care into the cultivation and use of plant or fungal matter. However, the contributions of the original discoverers can be lost as the natural products are developed into pharmaceutical products.
{"title":"The original caretakers of salvinorin A and recognizing Indigenous contributions to science","authors":"Khalyd J. Clay, Ryan A. Shenvi","doi":"10.1038/s41557-024-01659-x","DOIUrl":"10.1038/s41557-024-01659-x","url":null,"abstract":"Much natural-product-based drug discovery has depended on the practices of Indigenous Peoples, who have sometimes invested centuries of care into the cultivation and use of plant or fungal matter. However, the contributions of the original discoverers can be lost as the natural products are developed into pharmaceutical products.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1735-1736"},"PeriodicalIF":19.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1038/s41557-024-01655-1
Bappaditya Chandra, Swarnendu Tripathi, Richard Kriwacki
Membraneless cellular assemblies termed biomolecular condensates — into which diverse biopolymers partition — mediate myriad biological processes. A study now reveals that physicochemical features, not specific stereochemistry, influence whether small molecules are enriched within or excluded from a diverse panel of condensates.
{"title":"Properties governing small-molecule partitioning into biomolecular condensates","authors":"Bappaditya Chandra, Swarnendu Tripathi, Richard Kriwacki","doi":"10.1038/s41557-024-01655-1","DOIUrl":"10.1038/s41557-024-01655-1","url":null,"abstract":"Membraneless cellular assemblies termed biomolecular condensates — into which diverse biopolymers partition — mediate myriad biological processes. A study now reveals that physicochemical features, not specific stereochemistry, influence whether small molecules are enriched within or excluded from a diverse panel of condensates.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1743-1745"},"PeriodicalIF":19.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1038/s41557-024-01652-4
David A. Rusling, Karen M. Vasquez
A method has been developed based on proximity labelling that detects the interaction of specific proteins with endogenous triplex DNA sequences formed in live cells — significantly expanding the catalogue of putative proteins that interact with these DNA structures.
我们开发了一种基于近距离标记的方法，可以检测特定蛋白质与活细胞中形成的内源性三重 DNA 序列的相互作用，从而大大扩展了与这些 DNA 结构相互作用的假定蛋白质的目录。
{"title":"A third strand for protein–DNA interactions","authors":"David A. Rusling, Karen M. Vasquez","doi":"10.1038/s41557-024-01652-4","DOIUrl":"10.1038/s41557-024-01652-4","url":null,"abstract":"A method has been developed based on proximity labelling that detects the interaction of specific proteins with endogenous triplex DNA sequences formed in live cells — significantly expanding the catalogue of putative proteins that interact with these DNA structures.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1748-1750"},"PeriodicalIF":19.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1038/s41557-024-01641-7
A. Daisley, J. S. J. Hargreaves
Although supported metal catalysts are active for ammonia synthesis, there is a need for catalysts that are active under milder reaction conditions. Now, fullerenes are shown to be convenient and multifunctional promoters for ammonia production that also eliminate hydrogen poisoning.
{"title":"Fullerenes promote transition-metal-catalysed ammonia synthesis","authors":"A. Daisley, J. S. J. Hargreaves","doi":"10.1038/s41557-024-01641-7","DOIUrl":"10.1038/s41557-024-01641-7","url":null,"abstract":"Although supported metal catalysts are active for ammonia synthesis, there is a need for catalysts that are active under milder reaction conditions. Now, fullerenes are shown to be convenient and multifunctional promoters for ammonia production that also eliminate hydrogen poisoning.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1739-1740"},"PeriodicalIF":19.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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