Pub Date : 2025-01-25DOI: 10.1016/j.cell.2025.01.020
Yiding Li, John J. Briguglio, Sandro Romani, Jeffrey C. Magee
(Cell 187, 6804–6819.e1–e21; November 27, 2024)
{"title":"Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3","authors":"Yiding Li, John J. Briguglio, Sandro Romani, Jeffrey C. Magee","doi":"10.1016/j.cell.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.020","url":null,"abstract":"(Cell <em>187</em>, 6804–6819.e1–e21; November 27, 2024)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"47 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030933","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}
Pub Date : 2025-01-24DOI: 10.1016/j.cell.2025.01.003
Hui Peng, Sergei Kotelnikov, Megan E. Egbert, Shany Ofaim, Grant C. Stevens, Sadhna Phanse, Tatiana Saccon, Mikhail Ignatov, Shubham Dutta, Zoe Istace, Mohamed Taha Moutaoufik, Hiroyuki Aoki, Neal Kewalramani, Jianxian Sun, Yufeng Gong, Dzmitry Padhorny, Gennady Poda, Andrey Alekseenko, Kathryn A. Porter, George Jones, Andrew Emili
Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces. This effort revealed principles governing functional crosstalk on a network level, divergent patterns of binding pocket conservation, and scaffolds for designing selective chemical probes. This structurally resolved ligand interactome mapping pipeline can be scaled to illuminate the native small-molecule networks of complete cells and potentially entire multi-cellular communities.
{"title":"Ligand interaction landscape of transcription factors and essential enzymes in E. coli","authors":"Hui Peng, Sergei Kotelnikov, Megan E. Egbert, Shany Ofaim, Grant C. Stevens, Sadhna Phanse, Tatiana Saccon, Mikhail Ignatov, Shubham Dutta, Zoe Istace, Mohamed Taha Moutaoufik, Hiroyuki Aoki, Neal Kewalramani, Jianxian Sun, Yufeng Gong, Dzmitry Padhorny, Gennady Poda, Andrey Alekseenko, Kathryn A. Porter, George Jones, Andrew Emili","doi":"10.1016/j.cell.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.003","url":null,"abstract":"Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium <em>Escherichia coli</em>. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces. This effort revealed principles governing functional crosstalk on a network level, divergent patterns of binding pocket conservation, and scaffolds for designing selective chemical probes. This structurally resolved ligand interactome mapping pipeline can be scaled to illuminate the native small-molecule networks of complete cells and potentially entire multi-cellular communities.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"34 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026665","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}
Biocatalytic cascades with spatial proximity can orchestrate multistep pathways to form metabolic highways, which enhance the overall catalytic efficiency. However, the effect of spatial organization on catalytic activity is poorly understood, and multienzyme architectural engineering with predictable performance remains unrealized. Here, we developed a standardized framework, called iMARS, to rapidly design the optimal multienzyme architecture by integrating high-throughput activity tests and structural analysis. The approach showed potential for industrial-scale applications, with artificial fusion enzymes designed by iMARS significantly improving the production of resveratrol by 45.1-fold and raspberry ketone by 11.3-fold in vivo, as well as enhancing ergothioneine synthesis in fed-batch fermentation. In addition, iMARS greatly enhanced the in vitro catalytic efficiency of the multienzyme complexes for PET plastic depolymerization and vanillin biosynthesis. As a generalizable and flexible strategy at molecular level, iMARS could greatly facilitate green chemistry, synthetic biology, and biomanufacturing.
{"title":"Rational multienzyme architecture design with iMARS","authors":"Jiawei Wang, Xingyu Ouyang, Shiyu Meng, Bowen Zhao, Liangxu Liu, Chaofeng Li, Hengrun Li, Haotian Zheng, Yihan Liu, Ting Shi, Yi-Lei Zhao, Jun Ni","doi":"10.1016/j.cell.2024.12.029","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.029","url":null,"abstract":"Biocatalytic cascades with spatial proximity can orchestrate multistep pathways to form metabolic highways, which enhance the overall catalytic efficiency. However, the effect of spatial organization on catalytic activity is poorly understood, and multienzyme architectural engineering with predictable performance remains unrealized. Here, we developed a standardized framework, called iMARS, to rapidly design the optimal multienzyme architecture by integrating high-throughput activity tests and structural analysis. The approach showed potential for industrial-scale applications, with artificial fusion enzymes designed by iMARS significantly improving the production of resveratrol by 45.1-fold and raspberry ketone by 11.3-fold <em>in vivo</em>, as well as enhancing ergothioneine synthesis in fed-batch fermentation. In addition, iMARS greatly enhanced the <em>in vitro</em> catalytic efficiency of the multienzyme complexes for PET plastic depolymerization and vanillin biosynthesis. As a generalizable and flexible strategy at molecular level, iMARS could greatly facilitate green chemistry, synthetic biology, and biomanufacturing.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"25 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020982","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2024.12.028
Wencheng Zhu, Juan Meng, Yan Li, Lei Gu, Wenjun Liu, Ziyi Li, Yi Shen, Xiaoyu Shen, Zihong Wang, Yonggen Wu, Guiquan Wang, Junfeng Zhang, Huiping Zhang, Haiyan Yang, Xi Dong, Hui Wang, Xuefeng Huang, Yidi Sun, Chen Li, Liangshan Mu, Zhen Liu
Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatomic data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts often contribute to protein accumulation in blastocysts. Using mouse embryos, we identified several transcriptional regulators critical for early development, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor-quality embryos from over 100 patient couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening avenues for addressing human infertility.
{"title":"Comparative proteomic landscapes elucidate human preimplantation development and failure","authors":"Wencheng Zhu, Juan Meng, Yan Li, Lei Gu, Wenjun Liu, Ziyi Li, Yi Shen, Xiaoyu Shen, Zihong Wang, Yonggen Wu, Guiquan Wang, Junfeng Zhang, Huiping Zhang, Haiyan Yang, Xi Dong, Hui Wang, Xuefeng Huang, Yidi Sun, Chen Li, Liangshan Mu, Zhen Liu","doi":"10.1016/j.cell.2024.12.028","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.028","url":null,"abstract":"Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatomic data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts often contribute to protein accumulation in blastocysts. Using mouse embryos, we identified several transcriptional regulators critical for early development, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor-quality embryos from over 100 patient couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening avenues for addressing human infertility.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"120 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020980","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2024.12.035
Erez Yirmiya, Samuel J. Hobbs, Azita Leavitt, Ilya Osterman, Carmel Avraham, Dina Hochhauser, Barak Madhala, Marharyta Skovorodka, Joel M.J. Tan, Hunter C. Toyoda, Igor Chebotar, Maxim Itkin, Sergey Malitsky, Gil Amitai, Philip J. Kranzusch, Rotem Sorek
Viruses encode proteins that inhibit host defenses, but sifting through the millions of available viral sequences for immune-modulatory proteins has been so far impractical. Here, we develop a process to systematically screen virus-encoded proteins for inhibitors that physically bind host immune proteins. Focusing on Thoeris and CBASS, bacterial defense systems that are the ancestors of eukaryotic Toll/interleukin-1 receptor (TIR) and cyclic GMP-AMP synthase (cGAS) immunity, we discover seven families of Thoeris and CBASS inhibitors, encompassing thousands of genes widespread in phages. Verified inhibitors exhibit extensive physical interactions with the respective immune protein counterpart, with all inhibitors blocking the active site of the immune protein. Remarkably, a phage-encoded inhibitor of bacterial TIR proteins can bind and inhibit distantly related human and plant immune TIRs, and a phage-derived inhibitor of bacterial cGAS-like enzymes can inhibit the human cGAS. Our results demonstrate that phages are a reservoir for immune-modulatory proteins capable of inhibiting bacterial, animal, and plant immunity.
{"title":"Structure-guided discovery of viral proteins that inhibit host immunity","authors":"Erez Yirmiya, Samuel J. Hobbs, Azita Leavitt, Ilya Osterman, Carmel Avraham, Dina Hochhauser, Barak Madhala, Marharyta Skovorodka, Joel M.J. Tan, Hunter C. Toyoda, Igor Chebotar, Maxim Itkin, Sergey Malitsky, Gil Amitai, Philip J. Kranzusch, Rotem Sorek","doi":"10.1016/j.cell.2024.12.035","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.035","url":null,"abstract":"Viruses encode proteins that inhibit host defenses, but sifting through the millions of available viral sequences for immune-modulatory proteins has been so far impractical. Here, we develop a process to systematically screen virus-encoded proteins for inhibitors that physically bind host immune proteins. Focusing on Thoeris and CBASS, bacterial defense systems that are the ancestors of eukaryotic Toll/interleukin-1 receptor (TIR) and cyclic GMP-AMP synthase (cGAS) immunity, we discover seven families of Thoeris and CBASS inhibitors, encompassing thousands of genes widespread in phages. Verified inhibitors exhibit extensive physical interactions with the respective immune protein counterpart, with all inhibitors blocking the active site of the immune protein. Remarkably, a phage-encoded inhibitor of bacterial TIR proteins can bind and inhibit distantly related human and plant immune TIRs, and a phage-derived inhibitor of bacterial cGAS-like enzymes can inhibit the human cGAS. Our results demonstrate that phages are a reservoir for immune-modulatory proteins capable of inhibiting bacterial, animal, and plant immunity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"17 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020984","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2025.01.019
Hao Song, Tianjiao Hao, Pu Han, Haichen Wang, Xu Zhang, Xiaomei Li, Yuxuan Wang, Jiamin Chen, Ying Li, Xiyue Jin, Xuefeng Duan, Wei Zhang, Yuhai Bi, Ronghua Jin, Lei Sun, Ningli Wang, George F. Gao
The ongoing circulation of highly pathogenic avian influenza (HPAI) A (H5N1) viruses, particularly clade 2.3.4.4b strains, poses a significant threat to animal and public health. Recent outbreaks in cattle highlight concerns about cross-species transmission and zoonotic spillover. Here, we found that the hemagglutinin (HA) protein from a cattle-infecting H5N1 virus has acquired slight binding to human-like α2-6-linked receptors while still exhibiting a strong preference for avian-like α2-3-linked sialic acid receptors. Immunohistochemical staining revealed HA binding to bovine pulmonary and mammary tissues, aligning with clinical observations. HA also binds effectively to human conjunctival, tracheal, and mammary tissues, indicating a risk for human transmission, notably in cases of conjunctivitis. High-resolution cryo-electron microscopy (cryo-EM) structures of this H5 HA in complex with either α2-3 or α2-6 receptors elucidate the molecular mechanisms underlying its receptor-binding properties. These findings provide critical insights into the tropism and transmission potential of this emerging pathogen.
高致病性禽流感（HPAI） A （H5N1）病毒的持续传播，特别是2.3.4.4b进化枝毒株，对动物和公众健康构成重大威胁。最近在牛中爆发的疫情突出了对跨物种传播和人畜共患病溢出的担忧。在这里，我们发现来自牛感染H5N1病毒的血凝素（HA）蛋白与人样α2-6连接受体轻微结合，但仍然对鸟样α2-3连接的唾液酸受体表现出强烈的偏好。免疫组织化学染色显示透明质酸与牛肺和乳腺组织结合，与临床观察相符。透明质酸还能与人类结膜、气管和乳腺组织有效结合，这表明它有人类传播的风险，特别是在结膜炎的情况下。该H5 HA与α2-3或α2-6受体复合物的高分辨率冷冻电镜（cryo-EM）结构阐明了其受体结合特性的分子机制。这些发现为了解这种新出现的病原体的倾向和传播潜力提供了重要的见解。
{"title":"Receptor binding, structure, and tissue tropism of cattle-infecting H5N1 avian influenza virus hemagglutinin","authors":"Hao Song, Tianjiao Hao, Pu Han, Haichen Wang, Xu Zhang, Xiaomei Li, Yuxuan Wang, Jiamin Chen, Ying Li, Xiyue Jin, Xuefeng Duan, Wei Zhang, Yuhai Bi, Ronghua Jin, Lei Sun, Ningli Wang, George F. Gao","doi":"10.1016/j.cell.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.019","url":null,"abstract":"The ongoing circulation of highly pathogenic avian influenza (HPAI) A (H5N1) viruses, particularly clade 2.3.4.4b strains, poses a significant threat to animal and public health. Recent outbreaks in cattle highlight concerns about cross-species transmission and zoonotic spillover. Here, we found that the hemagglutinin (HA) protein from a cattle-infecting H5N1 virus has acquired slight binding to human-like α2-6-linked receptors while still exhibiting a strong preference for avian-like α2-3-linked sialic acid receptors. Immunohistochemical staining revealed HA binding to bovine pulmonary and mammary tissues, aligning with clinical observations. HA also binds effectively to human conjunctival, tracheal, and mammary tissues, indicating a risk for human transmission, notably in cases of conjunctivitis. High-resolution cryo-electron microscopy (cryo-EM) structures of this H5 HA in complex with either α2-3 or α2-6 receptors elucidate the molecular mechanisms underlying its receptor-binding properties. These findings provide critical insights into the tropism and transmission potential of this emerging pathogen.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020985","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2024.12.030
Zhonghua Liu, Tsan Sam Xiao
Plasma membrane rupture during lytic cell death was previously believed to occur through passive osmosis that burst open the membrane. Recent publications, including one in this issue of Cell, suggest that plasma membrane rupture is an active process mediated by ninjurin-1 (NINJ1) oligomers that dissolve membranes and/or assemble large pores.
{"title":"Rings of death: How NINJ1 executes plasma membrane rupture","authors":"Zhonghua Liu, Tsan Sam Xiao","doi":"10.1016/j.cell.2024.12.030","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.030","url":null,"abstract":"Plasma membrane rupture during lytic cell death was previously believed to occur through passive osmosis that burst open the membrane. Recent publications, including one in this issue of <em>Cell</em>, suggest that plasma membrane rupture is an active process mediated by ninjurin-1 (NINJ1) oligomers that dissolve membranes and/or assemble large pores.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020987","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2024.12.015
Eric Wang, Alexander A. Cohen, Luis F. Caldera, Jennifer R. Keeffe, Annie V. Rorick, Yusuf M. Adia, Priyanthi N.P. Gnanapragasam, Pamela J. Bjorkman, Arup K. Chakraborty
Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2COMs), five (mosaic-5COM), or seven (mosaic-7COM) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges. Naive and COVID-19 pre-vaccinated mice immunized with mosaic-7COM elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2COMs and mosaic-5COM elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.
{"title":"Designed mosaic nanoparticles enhance cross-reactive immune responses in mice","authors":"Eric Wang, Alexander A. Cohen, Luis F. Caldera, Jennifer R. Keeffe, Annie V. Rorick, Yusuf M. Adia, Priyanthi N.P. Gnanapragasam, Pamela J. Bjorkman, Arup K. Chakraborty","doi":"10.1016/j.cell.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.015","url":null,"abstract":"Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2<sub>COM</sub>s), five (mosaic-5<sub>COM</sub>), or seven (mosaic-7<sub>COM</sub>) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges. Naive and COVID-19 pre-vaccinated mice immunized with mosaic-7<sub>COM</sub> elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2<sub>COM</sub>s and mosaic-5<sub>COM</sub> elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7<sub>COM</sub>. However, mosaic-7<sub>COM</sub> elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"71 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021070","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2024.12.033
John W. Pham
Section snippets
Main text
If you’re reading this editorial, it’s 2025, or later, perhaps. I’m typing these words as 2024 is winding down. It’s getting close to the end of December, and some of my colleagues at Cell Press have already shut down their computers for some much needed and deserved time off. I will close my computer soon, too. I’ll spend time with friends and family, spoil my dogs, and eat too much. But right now, before turning the page on 2024, there’s one last thing I want to do, and that is to look back
{"title":"Cell after 50","authors":"John W. Pham","doi":"10.1016/j.cell.2024.12.033","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.033","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>If you’re reading this editorial, it’s 2025, or later, perhaps. I’m typing these words as 2024 is winding down. It’s getting close to the end of December, and some of my colleagues at Cell Press have already shut down their computers for some much needed and deserved time off. I will close my computer soon, too. I’ll spend time with friends and family, spoil my dogs, and eat too much. But right now, before turning the page on 2024, there’s one last thing I want to do, and that is to look back</section></section>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"57 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021106","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}
Pub Date : 2025-01-23DOI: 10.1016/j.cell.2025.01.004
Ming Zhang, Juan Feng, Chun Xie, Nan Song, Chaozhi Jin, Jian Wang, Qun Zhao, Lihua Zhang, Boshuang Wang, Yidi Sun, Fei Guo, Yang Li, Shujia Zhu
The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo.
{"title":"Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus","authors":"Ming Zhang, Juan Feng, Chun Xie, Nan Song, Chaozhi Jin, Jian Wang, Qun Zhao, Lihua Zhang, Boshuang Wang, Yidi Sun, Fei Guo, Yang Li, Shujia Zhu","doi":"10.1016/j.cell.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.004","url":null,"abstract":"The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving <em>N</em>-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs <em>in vivo</em>.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"33 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020983","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：