{"title":"Oxygen isotope composition of Mesoproterozoic (~1360 Ma) seawater constrained by clumped isotopes of North China limestones","authors":"Pingping Li, Fang Hao, Shijie He, Haobo Chai, Yongfei Jiao, Yaxuan Gao, Huayao Zou","doi":"10.1126/sciadv.adu6693","DOIUrl":"10.1126/sciadv.adu6693","url":null,"abstract":"<div >The oxygen isotope composition (δ<sup>18</sup>O) of Phanerozoic seawater has been widely investigated, but the δ<sup>18</sup>O values of Precambrian seawater remain poorly constrained, with ongoing debate over whether they were substantially lower than those of Phanerozoic seawater. To address this question, we analyzed the clumped isotopes of limestones from the North China Craton to reconstruct Mesoproterozoic seawater temperature and δ<sup>18</sup>O values. Our results indicate that the Mesoproterozoic seawater had a temperature of 26.9° ± 0.4°C and a δ<sup>18</sup>O value of −6.3 ± 0.2 per mil (relative to standard mean ocean water). This δ<sup>18</sup>O estimate aligns with previous inferences from geochemical modeling, marine iron oxides, and oxygen isotope ensembles, supporting the hypothesis that Mesoproterozoic seawater was isotopically lighter than its Phanerozoic counterpart. These findings provide insights into the Earth’s paleoclimate and the evolution of seawater composition during the Mesoproterozoic era.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu6693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adw1410
Céline Pattaroni, Matthew Macowan, Roxanne Chatzis, Giulia Iacono, Bailey Cardwell, Mindy Gore, Adnan Custovic, Michael D. Shields, Ultan F. Power, Jonathan Grigg, Graham Roberts, Peter Ghazal, Jürgen Schwarze, Steve Turner, Andrew Bush, Sejal Saglani, Clare M. Lloyd, Benjamin J. Marsland
{"title":"Bacterial communities co-develop with respiratory immunity early in life, linking dysbiosis to systemic monocyte signature and wheezing","authors":"Céline Pattaroni, Matthew Macowan, Roxanne Chatzis, Giulia Iacono, Bailey Cardwell, Mindy Gore, Adnan Custovic, Michael D. Shields, Ultan F. Power, Jonathan Grigg, Graham Roberts, Peter Ghazal, Jürgen Schwarze, Steve Turner, Andrew Bush, Sejal Saglani, Clare M. Lloyd, Benjamin J. Marsland","doi":"10.1126/sciadv.adw1410","DOIUrl":"10.1126/sciadv.adw1410","url":null,"abstract":"<div >Early microbial colonization influences respiratory disease risk, yet mechanisms remain unclear. In a prospective birth cohort of 256 infants, we profiled bacterial, fungal, and viral communities in the upper airway and assessed local immune gene expression longitudinally and systemic gene expression at 1 year. Bacterial populations, not fungal or viral, correlated most strongly with immune development during the first 3 months, coinciding with composition shifts and immune-related gene expression changes, including interferon and adaptive immunity pathways. In contrast, the mycobiome and resident viruses showed no significant coevolution with host immunity. By 1 year, infants who previously wheezed displayed an upper airway microbiota enriched in <i>Haemophilus influenzae</i> and <i>Moraxella</i>, accompanied by a distinct local and systemic immune gene signature featuring elevated classical monocyte-related genes. These findings reveal a specific link between early-life bacterial dysbiosis, monocyte-related immunity, and wheezing onset, suggesting potential targets for early intervention in respiratory disease.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw1410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adx7672
Pierre Duquesne, Céline Aoun, Mathieu Kurowska, Brieuc P. Perot, Kerui Zhang, Mounia Debili, Mirjana Weimershaus, François-Xavier Mauvais, Nicolas Cagnard, Nicolas Goudin, Bernardita Medel, Juan Eduardo Montero-Hermández, Linda Diedhiou, Jian-Dong Huang, Alain Fischer, Geneviève de Saint Basile, Mickaël M. Ménager, Pablo Vargas, Fernando E. Sepulveda, Gaël Ménasché
{"title":"Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration","authors":"Pierre Duquesne, Céline Aoun, Mathieu Kurowska, Brieuc P. Perot, Kerui Zhang, Mounia Debili, Mirjana Weimershaus, François-Xavier Mauvais, Nicolas Cagnard, Nicolas Goudin, Bernardita Medel, Juan Eduardo Montero-Hermández, Linda Diedhiou, Jian-Dong Huang, Alain Fischer, Geneviève de Saint Basile, Mickaël M. Ménager, Pablo Vargas, Fernando E. Sepulveda, Gaël Ménasché","doi":"10.1126/sciadv.adx7672","DOIUrl":"10.1126/sciadv.adx7672","url":null,"abstract":"<div >Dendritic cells (DCs) are professional antigen (Ag)–presenting cells that excel in initiating adaptive immune responses by continuously scanning peripheral tissues for Ags. To facilitate efficient DC migration, constant cross-talk between actin and microtubules is required to coordinate cytoskeletal networks and actomyosin contractility, but the related mechanisms have not been extensively characterized. We show that mouse DCs lacking Kif5b (the heavy chain of kinesin-1) exhibit a major impairment in cell migration in vivo and in vitro. Mechanistically, kinesin-1 coordinates cytoskeletal cross-talk between actin and microtubules during DC migration by modulating negatively RhoA activity through its interaction with GEF-H1, thereby limiting GEF-H1’s availability in the cytosol. The same mechanism operates in human primary monocyte–derived DCs and regulates efficient migration in a confined environment. Thus, our results highlight kinesin-1 as a key regulator of DC migration, through its coordinated control of cytoskeletal dynamics.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx7672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adx3050
Ayush Kumar, Kensei Kishimoto, Hira L. Goel, Christi A. Silva, Rui Li, Brendan Pacheco, Lihua J. Zhu, William A. Flavahan, Arthur M. Mercurio
{"title":"Resistance to radiation enhances metastasis by altering RNA metabolism","authors":"Ayush Kumar, Kensei Kishimoto, Hira L. Goel, Christi A. Silva, Rui Li, Brendan Pacheco, Lihua J. Zhu, William A. Flavahan, Arthur M. Mercurio","doi":"10.1126/sciadv.adx3050","DOIUrl":"10.1126/sciadv.adx3050","url":null,"abstract":"<div >The cellular programs that mediate therapy resistance are often important drivers of metastasis, a phenomenon that needs to be understood better to improve screening and treatment options for patients with cancer. Although this issue has been studied extensively for chemotherapy, less is known about a causal link between resistance to radiation therapy and metastasis. We investigated this problem in triple-negative breast cancer and established that radiation-resistant tumor cells have enhanced metastatic capacity. Resistance to radiation increases the expression of integrin β3 (<i>ITGB3</i>), which promotes enhanced migration and invasion. Bioinformatic analysis and subsequent experimentation revealed an enrichment of RNA metabolism pathways that stabilize <i>ITGB3</i> transcripts. Specifically, the RNA binding protein heterogeneous nuclear ribonucleoprotein L (<i>HNRNPL</i>), whose expression is regulated by Nrf2, mediates the formation of circular RNAs that sponge the family of let-7 microRNAs that target <i>ITGB3</i>. Collectively, our findings identify a mechanism of radiation-induced metastasis that is driven by alterations in RNA metabolism.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx3050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adz1415
Yingjie Song, Xiyu Wu, Bo Song, Ziqi Zhu, Derong Dai, Qinqin Ma, Rui Bao
{"title":"A choline-sensing regulator coordinates metabolic adaptation and pathogenesis in Pseudomonas aeruginosa pulmonary infections","authors":"Yingjie Song, Xiyu Wu, Bo Song, Ziqi Zhu, Derong Dai, Qinqin Ma, Rui Bao","doi":"10.1126/sciadv.adz1415","DOIUrl":"10.1126/sciadv.adz1415","url":null,"abstract":"<div ><i>Pseudomonas aeruginosa</i> exploits host-derived phosphatidylcholine (PC) to establish persistent lung infections, yet the mechanistic link between metabolic adaptation and pathogenesis remains unclear. Here, we demonstrate that choline (Cho)–induced regulator (CodR), a GcvA-type transcriptional regulator, serves as a master regulator integrating virulence, antibiotic resistance, and PC catabolism during pulmonary infection. CodR directly binds Cho, the key metabolite of PC degradation, to activate <i>pchP</i> and <i>norA</i>, facilitating exogenous PC/Cho utilization. Genome-wide profiling reveals that CodR targets conserved motifs in promoters of <i>mexA</i>, <i>pslA</i>, and <i>amrZ</i>, synchronizing virulence and tolerance pathways. <i>codR</i> deletion attenuated biofilm formation, type III secretion system activity, siderophore production, and PC catabolism, reducing bacterial pathogenicity in a murine pneumonia model. Notably, Cho/PC pretreatment potentiates CodR-dependent transcriptional activation of antibiotic resistance genes, elevating tolerance to ciprofloxacin and meropenem. Our findings elucidate a paradigm wherein <i>P. aeruginosa</i> co-opts host-derived Cho via CodR to simultaneously potentiate virulence and antibiotic resilience, exposing CodR as a druggable node to break infection-resistance synergies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adz1415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adx8771
Atsuki Nakano, Jun-ichi Kishikawa, Nishida Yui, Kyosuke Sugawara, Yuto Kan, Christoph Gerle, Hideki Shigematsu, Kaoru Mitsuoka, Ken Yokoyama
{"title":"Structures of rotary ATP synthase from Thermus thermophilus during proton powered ATP synthesis","authors":"Atsuki Nakano, Jun-ichi Kishikawa, Nishida Yui, Kyosuke Sugawara, Yuto Kan, Christoph Gerle, Hideki Shigematsu, Kaoru Mitsuoka, Ken Yokoyama","doi":"10.1126/sciadv.adx8771","DOIUrl":"10.1126/sciadv.adx8771","url":null,"abstract":"<div >ATP synthases are rotary molecular machines that use the proton motive force to rotate the central rotor complex relative to the surrounding stator apparatus, thereby coupling the ATP synthesis. We reconstituted the V/A-ATPase into liposomes and performed structural analysis using cryo-EM under conditions where the proton motive force was applied in the presence of ADP and Pi. ATP molecules were bound at two of the three catalytic sites of V/A-ATPase, confirming that the structure represents a state adopted during ATP synthesis. In this structure, the catalytic site closes upon binding of ADP and Pi through an induced fit mechanism. Multiple structures were obtained where the membrane-embedded rotor ring was in a different position relative to the stator. By comparing these structures, we found that torsion occurs in both the central rotor and the peripheral stator during 31° rotation of rotor ring. These structural snapshots of V/A-ATPase provide crucial insights into the mechanism of rotary catalysis of ATP synthesis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx8771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CysMP reveals metal ion–specific metalloproteomes and copper-regulated PGK1 activity in glycolysis","authors":"Yamei Yuan, Zhiyuan Wang, Chenfang Si, Jianlong Li, Fandong Ren, Yi Yuan, Ziqi Shi, Nana Sun, Xiaonuo Ma, Xingbang Dai, Yunxia Li, Yixiao Zhang, Jianping Liu, Hongbin Wang, Zhengjiang Zhu, Bing Shan, Yaoyang Zhang","doi":"10.1126/sciadv.adx7035","DOIUrl":"10.1126/sciadv.adx7035","url":null,"abstract":"<div >Metal ions are essential in regulating protein functions through interactions with residues such as cysteine, but comprehensive mapping of metal-specific metalloproteomes in mammals remains limited. Here, we introduce CysMP, a cysteine-centered metalloprotein profiling strategy to profile the metalloproteomes of 11 key metal ions. CysMP identified 8895 metal-binding sites across 4150 proteins, enabling quantitative comparisons between different metals and revealing both their binding promiscuity and preferences. Notably, zinc and copper ions exhibit the broadest protein interaction profiles. CysMP uncovers numerous potential metalloproteins. We demonstrate that copper and zinc bind to and inhibit 5′-methylthioadenosine phosphorylase, resulting in the accumulation of 5′-methylthioadenosine. Furthermore, copper binding suppresses phosphoglycerate kinase 1 activity, leading to a down-regulation of glycolysis. Our work not only establishes a valuable resource for a dual-specific metalloproteome database but also paves the way for understanding the molecular insights of metalloprotein functions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx7035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adz1726
Elan L’Estrange-Stranieri, Timothy A. Gottschalk, Anne M. Kong, Mhairi J. Maxwell, Ee Shan Pang, Evelyn Tsantikos, David M. Tarlinton, Meredith O’Keeffe, Mark D. Wright, Margaret L. Hibbs
{"title":"Lyn restrains lupus via kinase-independent mechanisms that limit Toll-like receptor activation and type I interferon responsiveness","authors":"Elan L’Estrange-Stranieri, Timothy A. Gottschalk, Anne M. Kong, Mhairi J. Maxwell, Ee Shan Pang, Evelyn Tsantikos, David M. Tarlinton, Meredith O’Keeffe, Mark D. Wright, Margaret L. Hibbs","doi":"10.1126/sciadv.adz1726","DOIUrl":"10.1126/sciadv.adz1726","url":null,"abstract":"<div >Lyn phosphorylates inhibitory immunoreceptors to terminate signaling; consequently, Lyn deficiency in mice causes hyperactive immune cells and lupus-like autoimmune disease. Lyn may also suppress autoimmunity independent of its kinase activity through inhibitory protein-protein binding interactions, although the importance of this mechanism is unclear. To analyze the kinase-independent functions of Lyn, mice expressing a catalytically inactive mutant of Lyn were generated and their phenotype compared to Lyn-deficient mice. Disease progression was blunted in Lyn kinase-dead mice indicating a contribution for kinase-independent Lyn functions in restraining autoantibody production, glomerulonephritis, Toll-like receptor signaling, and splenomegaly. Further comparative analyses identified an exclusive role for the kinase-dependent functions of Lyn in regulating B cell receptor signaling, dendritic cell phenotype, and type I interferon production. By contrast, interferon-stimulated gene expression and the regulation of thymic epithelial cell development and T cell selection are previously unidentified, exclusively kinase-independent functions for Lyn. Collectively, these findings further our understanding of the nuanced roles of Lyn in health and disease.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adz1726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.adw3717
Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G. Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A. Lewis, Farid Ullah, Thomas Arbogast, Jackson P. Ogden, Madeleine Harion, Marjolaine Willems, Maha S. Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R. Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E. Davis
{"title":"CEP76 impairment at the centrosome-cilium interface contributes to a spectrum of ciliopathies","authors":"Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G. Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A. Lewis, Farid Ullah, Thomas Arbogast, Jackson P. Ogden, Madeleine Harion, Marjolaine Willems, Maha S. Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R. Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E. Davis","doi":"10.1126/sciadv.adw3717","DOIUrl":"10.1126/sciadv.adw3717","url":null,"abstract":"<div >Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in <i>CEP76</i>, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish <i>cep76</i> mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including ALMS1 and LUZP1. Together, these findings expand the role of CEP76 beyond centriole duplication to include ciliary assembly and trafficking, establishing it as a ciliopathy gene. This work provides mechanistic insights into <i>CEP76</i>-related disease and broadens our understanding of centrosome-cilium biology.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw3717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science AdvancesPub Date : 2025-10-17DOI: 10.1126/sciadv.ady0499
Madan Kumar Shankar, Lukas Grunewald, Weixiao Yuan Wahlgren, Brigitte Stucki-Buchli, Amke Nimmrich, Moona Kurttila, Anna-Lena Fischer, Giacomo Salvadori, Andrea Cellini, Piotr Maj, Atsarina Larasati Anindya, Elin Claesson, Fangjia Luo, Tek Narsingh Malla, Suraj Pandey, Takehiko Tosha, Nuemket Nipawan, Shigeki Owada, Kensuke Tono, Rie Tanaka, Emina A. Stojković, Dmitry Mozorov, Pasi Myllyperkiö, Tatu Kumpulainen, Heikki Takala, Marius Schmidt, Janne A. Ihalainen, Sebastian Westenhoff
{"title":"Ultrafast, remote-controlled protonation reaction enables structural changes in a phytochrome","authors":"Madan Kumar Shankar, Lukas Grunewald, Weixiao Yuan Wahlgren, Brigitte Stucki-Buchli, Amke Nimmrich, Moona Kurttila, Anna-Lena Fischer, Giacomo Salvadori, Andrea Cellini, Piotr Maj, Atsarina Larasati Anindya, Elin Claesson, Fangjia Luo, Tek Narsingh Malla, Suraj Pandey, Takehiko Tosha, Nuemket Nipawan, Shigeki Owada, Kensuke Tono, Rie Tanaka, Emina A. Stojković, Dmitry Mozorov, Pasi Myllyperkiö, Tatu Kumpulainen, Heikki Takala, Marius Schmidt, Janne A. Ihalainen, Sebastian Westenhoff","doi":"10.1126/sciadv.ady0499","DOIUrl":"10.1126/sciadv.ady0499","url":null,"abstract":"<div >In photoactive proteins, coupling between the chromophore and protein matrix is exquisitely tuned. Proton transfer reactions can mediate this coupling, as in proton-coupled electron transfer and excited-state proton transfer. Additional mechanisms involving proton dislocations may exist but remain undiscovered. Here, we present a femtosecond crystallographic movie of the phytochrome from <i>Deinococcus radiodurans</i>. The structures reveal a space-conserving mechanism for rotation of the D-ring in the excited state. We observe rearrangement of a conserved hydrogen bond network within 300 fs, which precedes the isomerization reaction of the chromophore. Aided by molecular modeling and independently confirmed by femtosecond infrared spectroscopy, we attribute these changes to a protonation shift of the strictly conserved histidine-260. Although this histidine lies close to the photoexcited π-orbitals of the chromophore, it is not directly part of them. We propose that this “remote-controlled” proton transfer relays photoexcitation near-instantaneously to the protein matrix. This mechanism may be widely used to transduce cofactor signals to their hosting enzymes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 42","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady0499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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