Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69864-5
Eun-Jung Kang, Jung-Ran Noh, Jae-Hoon Kim, Ji Ah Park, Jeong-Pin Ahn, Min-Chan Kim, Jung Hyeon Choi, Young-Keun Choi, In-Bok Lee, Dong-Hee Choi, Yun Jeong Seo, Yoon Seok Jung, Kyoung-Shim Kim, Jung Hwan Hwang, Yong-Bum Kim, Jong-Soo Lee, Bon Jeong Ku, Jin-Ok Jeong, Hueng-Sik Choi, Jinhyun Kim, Yong-Hoon Kim, Chul-Ho Lee
{"title":"Small heterodimer partner protects against osteoarthritis by inhibiting IKKβ/NF-κB-mediated matrix-degrading enzymes in chondrocytes","authors":"Eun-Jung Kang, Jung-Ran Noh, Jae-Hoon Kim, Ji Ah Park, Jeong-Pin Ahn, Min-Chan Kim, Jung Hyeon Choi, Young-Keun Choi, In-Bok Lee, Dong-Hee Choi, Yun Jeong Seo, Yoon Seok Jung, Kyoung-Shim Kim, Jung Hwan Hwang, Yong-Bum Kim, Jong-Soo Lee, Bon Jeong Ku, Jin-Ok Jeong, Hueng-Sik Choi, Jinhyun Kim, Yong-Hoon Kim, Chul-Ho Lee","doi":"10.1038/s41467-026-69864-5","DOIUrl":"https://doi.org/10.1038/s41467-026-69864-5","url":null,"abstract":"","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"97 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69903-1
Tomoya Honda, Sora Yu, Dung Mai, Leo Baumgart, Emory M. Chan, Gyorgy Babnigg, Yasuo Yoshikuni
{"title":"CRAGE-RB-PI-seq reveals transcriptional dynamics of plant-associated bacteria during root colonization","authors":"Tomoya Honda, Sora Yu, Dung Mai, Leo Baumgart, Emory M. Chan, Gyorgy Babnigg, Yasuo Yoshikuni","doi":"10.1038/s41467-026-69903-1","DOIUrl":"https://doi.org/10.1038/s41467-026-69903-1","url":null,"abstract":"","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"46 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69900-4
Somya Vats, Pedro Dionisio, Quentin Lemercier, Raphael Pineau, Ludivine Therreau, Joanna Lipecka, Béatrice Cholley, Jean-Baptiste Moog, Jose Wojnacki, Céline Keime, Diana Zala, Philippe Bun, Sofia Freire, Neuza Domingues, Lydia Danglot, Ida Chiara Guerrera, Cédric Delevoye, Eric Chevet, Nuno Raimundo, Thierry Galli
Late endosomal secretion is an unconventional secretion mechanism that depends on the SNARE protein VAMP7. We previously showed that VAMP7 mediates the secretion of the ER protein Reticulon3. However, the functional relevance and molecular mechanism of this secretory pathway remain unclear. Here, we show that VAMP7 knockout cells exhibit impaired secretion of ER- and mitochondrial-derived proteins and signs of ER and mitochondrial stress. In addition, pharmacological induction of organellar stress enhances the VAMP7-dependent secretion. We assess the pathophysiological significance of this mechanism using a preclinical glioblastoma model. VAMP7 knockout glioblastoma cells implanted in male rat brain develop into more necrotic tumors with reduced macrophage infiltration compared to controls, suggesting that VAMP7-dependent late endosomal secretion contributes to the tumor microenvironment and affects macrophage infiltration. Together, our results support a model in which late endosomal secretion functions as an organelle quality-control and stress-communication mechanism, with particular relevance to cancer.
{"title":"VAMP7-dependent late endosomal secretion of ER and mitochondrial proteins impacts the tumor microenvironment and macrophage engagement","authors":"Somya Vats, Pedro Dionisio, Quentin Lemercier, Raphael Pineau, Ludivine Therreau, Joanna Lipecka, Béatrice Cholley, Jean-Baptiste Moog, Jose Wojnacki, Céline Keime, Diana Zala, Philippe Bun, Sofia Freire, Neuza Domingues, Lydia Danglot, Ida Chiara Guerrera, Cédric Delevoye, Eric Chevet, Nuno Raimundo, Thierry Galli","doi":"10.1038/s41467-026-69900-4","DOIUrl":"https://doi.org/10.1038/s41467-026-69900-4","url":null,"abstract":"Late endosomal secretion is an unconventional secretion mechanism that depends on the SNARE protein VAMP7. We previously showed that VAMP7 mediates the secretion of the ER protein Reticulon3. However, the functional relevance and molecular mechanism of this secretory pathway remain unclear. Here, we show that VAMP7 knockout cells exhibit impaired secretion of ER- and mitochondrial-derived proteins and signs of ER and mitochondrial stress. In addition, pharmacological induction of organellar stress enhances the VAMP7-dependent secretion. We assess the pathophysiological significance of this mechanism using a preclinical glioblastoma model. VAMP7 knockout glioblastoma cells implanted in male rat brain develop into more necrotic tumors with reduced macrophage infiltration compared to controls, suggesting that VAMP7-dependent late endosomal secretion contributes to the tumor microenvironment and affects macrophage infiltration. Together, our results support a model in which late endosomal secretion functions as an organelle quality-control and stress-communication mechanism, with particular relevance to cancer.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"284 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69709-1
Trevyn F. Q. Larson, Sarah Garcia Jones, Tamás Kalmár, Pablo Aramburu Sanchez, Sai Pavan Chitta, Varun Verma, Kristen L. Genter, Stephen T. Gill, Katarina Cicak, Sae Woo Nam, Gergö Fülöp, Jens Koch, Raymond W. Simmonds, András Gyenis
{"title":"Localized quasiparticles in a fluxonium with quasi-two-dimensional amorphous kinetic inductors","authors":"Trevyn F. Q. Larson, Sarah Garcia Jones, Tamás Kalmár, Pablo Aramburu Sanchez, Sai Pavan Chitta, Varun Verma, Kristen L. Genter, Stephen T. Gill, Katarina Cicak, Sae Woo Nam, Gergö Fülöp, Jens Koch, Raymond W. Simmonds, András Gyenis","doi":"10.1038/s41467-026-69709-1","DOIUrl":"https://doi.org/10.1038/s41467-026-69709-1","url":null,"abstract":"","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"31 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69490-1
Rebecca Meelker González, Sophia Laposchan, Erik Riedel, Anna Fürst, Naomi O’Sullivan, Wassim Gabriel, Mathias Wilhelm, Percy A. Knolle, Guillaume Médard, Bernhard Kuster, Chien-Yun Lee
Citrullination is a post-translational modification implicated in autoimmune and inflammatory diseases, yet its low abundance and lack of effective enrichment tools have limited proteome-wide analysis. Here, we develop a robust chemical proteomics workflow with improved specificity and throughput. This method builds upon glyoxal-based derivatization and incorporates a cleavable biotin linker for efficient peptide enrichment, release, and identification via mass spectrometry. Benchmarking demonstrates a > 10-fold increase in the detection of citrullinated peptides at sub-0.1% abundance. Applying this workflow to primary human neutrophils, we successfully monitor dynamic regulation, quantifying dose-dependent activation and inhibition by the PAD4 inhibitor GSK484. Furthermore, stimulation with the fungal pathogen Candida albicans reveals a “core citrullinome” conserved across distinct stimuli. Notably, extensive citrullination of linker histone H1 and structural proteins like lamin B1 suggests broad remodeling of cell architecture during NET formation. This workflow enables proteome-wide mapping of citrullination sites and facilitates its study across diverse biological contexts.
{"title":"High-throughput chemical proteomics workflow for profiling protein citrullination dynamics","authors":"Rebecca Meelker González, Sophia Laposchan, Erik Riedel, Anna Fürst, Naomi O’Sullivan, Wassim Gabriel, Mathias Wilhelm, Percy A. Knolle, Guillaume Médard, Bernhard Kuster, Chien-Yun Lee","doi":"10.1038/s41467-026-69490-1","DOIUrl":"https://doi.org/10.1038/s41467-026-69490-1","url":null,"abstract":"Citrullination is a post-translational modification implicated in autoimmune and inflammatory diseases, yet its low abundance and lack of effective enrichment tools have limited proteome-wide analysis. Here, we develop a robust chemical proteomics workflow with improved specificity and throughput. This method builds upon glyoxal-based derivatization and incorporates a cleavable biotin linker for efficient peptide enrichment, release, and identification via mass spectrometry. Benchmarking demonstrates a > 10-fold increase in the detection of citrullinated peptides at sub-0.1% abundance. Applying this workflow to primary human neutrophils, we successfully monitor dynamic regulation, quantifying dose-dependent activation and inhibition by the PAD4 inhibitor GSK484. Furthermore, stimulation with the fungal pathogen <jats:italic>Candida albicans</jats:italic> reveals a “core citrullinome” conserved across distinct stimuli. Notably, extensive citrullination of linker histone H1 and structural proteins like lamin B1 suggests broad remodeling of cell architecture during NET formation. This workflow enables proteome-wide mapping of citrullination sites and facilitates its study across diverse biological contexts.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"174 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aqueous Zn | |I 2 batteries, involving I - /I 0 /I + redox, are promising yet usually facing low I 2 utilization dominated by I 0 /I + redox, especially under high loadings. Unlocking alternative pathway to I 0 /I + redox, preferably in noncorrosive dilute electrolytes, is a crucial solution. Here, we report a pathway towards more thermodynamically favorable I 0 /I + redox, via a unique carbon-halogen bond substitution. This pathway is realized with a low-concentrated (0.7 M), noncorrosive organohalide additive (2-bromoacetamide, BrAce), triggering a reversible Br-C···I (0) and C-I (+) -Br bond substitution. Compared with conventional interhalogen bonding (I-Br) pathway, this pathway synchronously lowers the barrier for I⁰/I⁺ redox and strengthens the anti-hydrolysis of I + species, by elaborately regulating axial δ hole activity of interhalogen bond (I (δ+) -Br). Notably, this pathway enables sustainable operation of four-electron Zn | |I 2 batteries with high I 2 loading (8.6 ~ 24.0 mg cm -2 ), featuring improved performances: (1) high I 2 utilizations (55% ~ 80%) at high rates (5.8 ~ 46.4 mA cm -2 ), (2) long lifespan ( $$ > $$> 400 cycles) with practical areal capacity ( ~ 3.85 mA h cm -2 ) and 99.5% retention even at 47.5 mA cm -2 . This pathway opens an exciting research direction to unlock unusual halogen chemistry for scalable, high-energy, sustainable aqueous batteries.
涉及I - /I 0 /I +氧化还原的水锌| | i2电池是很有前途的，但通常面临以I 0 /I +氧化还原为主的低I 2利用率，特别是在高负荷下。解锁i0 /I +氧化还原的替代途径，最好是在无腐蚀性的稀释电解质中，是一个关键的解决方案。在这里，我们报告了一种通过独特的碳卤素键取代实现热力学上更有利的I 0 /I +氧化还原的途径。该途径通过低浓度（0.7 M）、无腐蚀性的有机卤化物添加剂（2-溴乙酰胺，BrAce）实现，引发可逆的Br-C···I(0)和C-I (+) -Br键取代。与传统的卤素间键（I-Br）途径相比，该途径通过精心调节卤素间键（I (δ+) -Br）的轴向δ孔活性，同步降低了I⁰/I⁺氧化还原的屏障，增强了I +物质的抗水解能力。值得注意的是，该途径能够实现高i2负载（8.6 24.0 mg cm -2）的四电子Zn | | i2电池的可持续运行，并具有改进的性能：(1)高i2利用率(55% ~ 80%) at high rates (5.8 ~ 46.4 mA cm -2 ), (2) long lifespan ( $$ > $$ > 400 cycles) with practical areal capacity ( ~ 3.85 mA h cm -2 ) and 99.5% retention even at 47.5 mA cm -2 . This pathway opens an exciting research direction to unlock unusual halogen chemistry for scalable, high-energy, sustainable aqueous batteries.
{"title":"Carbon-halogen bond substitution enables high-utilization four-electron iodine redox in noncorrosive dilute electrolytes","authors":"Zhiheng Shi, Yongchao Tang, Yue Wei, Guigui Liu, Haolong Huang, Jintu Qi, Zhenfeng Feng, Minghui Ye, Yufei Zhang, Zhipeng Wen, Xiaoqing Liu, Qi Yang, Chunyi Zhi, Cheng Chao Li","doi":"10.1038/s41467-026-69743-z","DOIUrl":"https://doi.org/10.1038/s41467-026-69743-z","url":null,"abstract":"Aqueous Zn | |I <jats:sub>2</jats:sub> batteries, involving I <jats:sup>-</jats:sup> /I <jats:sup>0</jats:sup> /I <jats:sup>+</jats:sup> redox, are promising yet usually facing low I <jats:sub>2</jats:sub> utilization dominated by I <jats:sup>0</jats:sup> /I <jats:sup>+</jats:sup> redox, especially under high loadings. Unlocking alternative pathway to I <jats:sup>0</jats:sup> /I <jats:sup>+</jats:sup> redox, preferably in noncorrosive dilute electrolytes, is a crucial solution. Here, we report a pathway towards more thermodynamically favorable I <jats:sup>0</jats:sup> /I <jats:sup>+</jats:sup> redox, via a unique carbon-halogen bond substitution. This pathway is realized with a low-concentrated (0.7 M), noncorrosive organohalide additive (2-bromoacetamide, BrAce), triggering a reversible Br-C···I <jats:sup>(0)</jats:sup> and C-I <jats:sup>(+)</jats:sup> -Br bond substitution. Compared with conventional interhalogen bonding (I-Br) pathway, this pathway synchronously lowers the barrier for I⁰/I⁺ redox and strengthens the anti-hydrolysis of I <jats:sup>+</jats:sup> species, by elaborately regulating axial δ hole activity of interhalogen bond (I <jats:sup>(δ+)</jats:sup> -Br). Notably, this pathway enables sustainable operation of four-electron Zn | |I <jats:sub>2</jats:sub> batteries with high I <jats:sub>2</jats:sub> loading (8.6 ~ 24.0 mg cm <jats:sup>-2</jats:sup> ), featuring improved performances: (1) high I <jats:sub>2</jats:sub> utilizations (55% ~ 80%) at high rates (5.8 ~ 46.4 mA cm <jats:sup>-2</jats:sup> ), (2) long lifespan ( <jats:inline-formula> <jats:alternatives> <jats:tex-math>$$ > $$</jats:tex-math> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"> <mml:mo>></mml:mo> </mml:math> </jats:alternatives> </jats:inline-formula> 400 cycles) with practical areal capacity ( ~ 3.85 mA h cm <jats:sup>-2</jats:sup> ) and 99.5% retention even at 47.5 mA cm <jats:sup>-2</jats:sup> . This pathway opens an exciting research direction to unlock unusual halogen chemistry for scalable, high-energy, sustainable aqueous batteries.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"49 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69880-5
Pierre Didier, Prakhar Jain, Mathieu Bertrand, Jost Kellner, Oliver Pitz, Zhecheng Dai, Tristan Kuttner, Mattias Beck, Baile Chen, Jérôme Faist, Rachel Grange
The mid-infrared spectrum, spanning from 3 to 14 µm, holds great promise for molecular spectroscopy and free space optical communication, benefiting from strong molecular absorption and reduced atmospheric attenuation. While progress in MIR photonics has accelerated due to improved sources and detectors, integrated low-loss, high -performance modulators remain limited. In order to address this gap, we demonstrate a broadband, high speed lithium niobate on sapphire Mach Zehnder electro optic modulator operating from 3.95 to 4.5 µm. The device shows a 3 dB bandwidth above 20 GHz, 17 dB extinction ratio, and VπL = 22 V ⋅ cm, with optical output power at the half milliwatt level. We demonstrate 10 Gbit s −1 data transmission and a 70 GHz broad frequency comb, uniquely combining integration, low propagation loss, extinction ratio and high-speed operation.
中红外光谱，跨度从3到14µm，对分子光谱和自由空间光通信具有很大的前景，受益于强分子吸收和减少大气衰减。虽然由于光源和探测器的改进，MIR光子学的进展已经加速，但集成的低损耗、高性能调制器仍然有限。为了解决这一差距，我们展示了一种宽带，高速铌酸锂蓝宝石Mach Zehnder电光调制器，工作范围为3.95至4.5µm。该器件带宽在20 GHz以上为3 dB，消光比为17 dB， V π L = 22 V⋅cm，光输出功率为半毫瓦级。我们展示了10gbit / s−1数据传输和70ghz宽频梳，独特地结合了集成、低传播损耗、消光比和高速运行。
{"title":"Thin film lithium niobate on sapphire for integrated mid-infrared modulator","authors":"Pierre Didier, Prakhar Jain, Mathieu Bertrand, Jost Kellner, Oliver Pitz, Zhecheng Dai, Tristan Kuttner, Mattias Beck, Baile Chen, Jérôme Faist, Rachel Grange","doi":"10.1038/s41467-026-69880-5","DOIUrl":"https://doi.org/10.1038/s41467-026-69880-5","url":null,"abstract":"The mid-infrared spectrum, spanning from 3 to 14 µm, holds great promise for molecular spectroscopy and free space optical communication, benefiting from strong molecular absorption and reduced atmospheric attenuation. While progress in MIR photonics has accelerated due to improved sources and detectors, integrated low-loss, high -performance modulators remain limited. In order to address this gap, we demonstrate a broadband, high speed lithium niobate on sapphire Mach Zehnder electro optic modulator operating from 3.95 to 4.5 µm. The device shows a 3 dB bandwidth above 20 GHz, 17 dB extinction ratio, and <jats:italic>V</jats:italic> <jats:sub> <jats:italic>π</jats:italic> </jats:sub> <jats:italic>L</jats:italic> = 22 V ⋅ cm, with optical output power at the half milliwatt level. We demonstrate 10 Gbit s <jats:sup>−1</jats:sup> data transmission and a 70 GHz broad frequency comb, uniquely combining integration, low propagation loss, extinction ratio and high-speed operation.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"24 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-21DOI: 10.1038/s41467-026-69782-6
Simon Maria Kienle, Matthias Sigg, Tobias Schneider, Katrin Stuber, Jan Lehmann, Jasmin Jansen, Florian Stengel, Andreas Marx, Michael Kovermann, Martin Scheffner
Lysine acetylation plays a prominent regulatory role in eukaryotic cells. Yet, determining the functional consequences of acetylation for a given protein represents a considerable challenge. For instance, lysine residues are subject to various posttranslational modifications, rendering interpretation of mutational studies difficult. The genetic code expansion technology enables site-specific incorporation of acetyllysine (AcK) into proteins, but the applicability of AcK is limited, as within cells, the acetyl group is removed by deacetylases. Here, we show that site-specific incorporation of the non-hydrolyzable AcK analog ketolysine (KeK) into ubiquitin closely resembles the structural and functional effects of AcK incorporation. Furthermore, AcK and KeK can be efficiently incorporated into the tumor suppressor p53 in cells. However, whereas AcK becomes deacetylated, KeK remains stable. Accordingly, incorporation of KeK, but not AcK, affects p53-mediated transcription. Thus, we propose that KeK is a well-suited AcK surrogate for studying acetylation of a given protein in cells.
{"title":"Non-hydrolyzable acetyllysine analogs to study protein acetylation in vitro and in cells","authors":"Simon Maria Kienle, Matthias Sigg, Tobias Schneider, Katrin Stuber, Jan Lehmann, Jasmin Jansen, Florian Stengel, Andreas Marx, Michael Kovermann, Martin Scheffner","doi":"10.1038/s41467-026-69782-6","DOIUrl":"https://doi.org/10.1038/s41467-026-69782-6","url":null,"abstract":"Lysine acetylation plays a prominent regulatory role in eukaryotic cells. Yet, determining the functional consequences of acetylation for a given protein represents a considerable challenge. For instance, lysine residues are subject to various posttranslational modifications, rendering interpretation of mutational studies difficult. The genetic code expansion technology enables site-specific incorporation of acetyllysine (AcK) into proteins, but the applicability of AcK is limited, as within cells, the acetyl group is removed by deacetylases. Here, we show that site-specific incorporation of the non-hydrolyzable AcK analog ketolysine (KeK) into ubiquitin closely resembles the structural and functional effects of AcK incorporation. Furthermore, AcK and KeK can be efficiently incorporated into the tumor suppressor p53 in cells. However, whereas AcK becomes deacetylated, KeK remains stable. Accordingly, incorporation of KeK, but not AcK, affects p53-mediated transcription. Thus, we propose that KeK is a well-suited AcK surrogate for studying acetylation of a given protein in cells.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"13 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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