Bacteriophages have evolved anti-CRISPR (Acr) proteins to combat the adaptive immunity provided by bacterial CRISPR–Cas systems. Here, we report the cryo-electron microscopy structure of an anti-Cas9 protein AcrIIA27 bound to SpyCas9–sgRNA (single guide RNA) complex. Our structure reveals that AcrIIA27 binds the solvent-exposed phosphate backbone of the sgRNA, acting as a potent inhibitor of diverse Cas9 orthologs. AcrIIA27 in the structure is positioned near the protospacer-adjacent motif DNA-binding pocket on SpyCas9, causing steric hindrance that prevents substrate DNA recognition. This mechanism suggests solvent-exposed regions of sgRNAs (PTP RNAs), prone to nonspecific binding of positively charged components, may compromise CRISPR–Cas genome-editing efficiency. Indeed, truncations of the PTP RNAs in different editing systems significantly enhance genome-editing efficiency in human cells. Overall, our findings reveal a previously uncharacterized inhibition mechanism of an anti-Cas protein and offers a general strategy for developing more efficient genome-editing tools. Yu, Yin, Zhu, Lu and colleagues show that Acr inhibits Cas activity through a scaffold RNA interaction and further develop an RNA truncation optimization strategy to enhance editing performance.
{"title":"An anti-CRISPR targets the sgRNA to block Cas9 and guides the design of enhanced genome editors","authors":"Ling Yu, Mingyu Yin, Yuwei Zhu, Zebin Lu, Bao Xiao, Fengxia Zhou, Yue Yu, Zhiwei Huang","doi":"10.1038/s41594-025-01741-z","DOIUrl":"10.1038/s41594-025-01741-z","url":null,"abstract":"Bacteriophages have evolved anti-CRISPR (Acr) proteins to combat the adaptive immunity provided by bacterial CRISPR–Cas systems. Here, we report the cryo-electron microscopy structure of an anti-Cas9 protein AcrIIA27 bound to SpyCas9–sgRNA (single guide RNA) complex. Our structure reveals that AcrIIA27 binds the solvent-exposed phosphate backbone of the sgRNA, acting as a potent inhibitor of diverse Cas9 orthologs. AcrIIA27 in the structure is positioned near the protospacer-adjacent motif DNA-binding pocket on SpyCas9, causing steric hindrance that prevents substrate DNA recognition. This mechanism suggests solvent-exposed regions of sgRNAs (PTP RNAs), prone to nonspecific binding of positively charged components, may compromise CRISPR–Cas genome-editing efficiency. Indeed, truncations of the PTP RNAs in different editing systems significantly enhance genome-editing efficiency in human cells. Overall, our findings reveal a previously uncharacterized inhibition mechanism of an anti-Cas protein and offers a general strategy for developing more efficient genome-editing tools. Yu, Yin, Zhu, Lu and colleagues show that Acr inhibits Cas activity through a scaffold RNA interaction and further develop an RNA truncation optimization strategy to enhance editing performance.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"318-329"},"PeriodicalIF":10.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003804","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 : 2026-01-13DOI: 10.1038/s41594-025-01708-0
Minji Kim, Ping Wang, Patricia A. Clow, Eli Chien, Xiaotao Wang, Jianhao Peng, Haoxi Chai, Xiyuan Liu, Byoungkoo Lee, Chew Yee Ngan, Olgica Milenkovic, Jeffrey H. Chuang, Chia-Lin Wei, Rafael Casellas, Albert W. Cheng, Yijun Ruan
Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely debated. Here we investigated the relationship between cohesin and RNA polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNA polymerase II and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific downregulated genes. By contrast, short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly constitutively expressed. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions in cohesin-depleted cells. Remarkably, RAD21 depletion appeared to upregulate genes that were involved in initiating DNA replication and disrupted DNA replication timing. Our results elucidate the multifaceted roles of cohesin in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes and maintaining timely DNA replication. Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.
{"title":"Interplay between cohesin and RNA polymerase II in regulating chromatin interactions and gene transcription","authors":"Minji Kim, Ping Wang, Patricia A. Clow, Eli Chien, Xiaotao Wang, Jianhao Peng, Haoxi Chai, Xiyuan Liu, Byoungkoo Lee, Chew Yee Ngan, Olgica Milenkovic, Jeffrey H. Chuang, Chia-Lin Wei, Rafael Casellas, Albert W. Cheng, Yijun Ruan","doi":"10.1038/s41594-025-01708-0","DOIUrl":"10.1038/s41594-025-01708-0","url":null,"abstract":"Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely debated. Here we investigated the relationship between cohesin and RNA polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNA polymerase II and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific downregulated genes. By contrast, short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly constitutively expressed. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions in cohesin-depleted cells. Remarkably, RAD21 depletion appeared to upregulate genes that were involved in initiating DNA replication and disrupted DNA replication timing. Our results elucidate the multifaceted roles of cohesin in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes and maintaining timely DNA replication. Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"259-274"},"PeriodicalIF":10.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956332","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 : 2026-01-08DOI: 10.1038/s41594-025-01736-w
Bin Chen, Guangchao Sun, Jake A. Kloeber, Huaping Xiao, Yaobin Ouyang, Fei Zhao, Ya Li, Shilin Xu, Sonja Dragojevic, Zheming Wu, Shouhai Zhu, Yiqun Han, Ping Yin, Xinyi Tu, Hongran Qin, Xiang Zhou, Kuntian Luo, Kevin L. Peterson, Jinzhou Huang, Taro Hitosugi, Haiming Dai, Min Deng, Robert W. Mutter, Zhenkun Lou
Okazaki fragment maturation requires efficient removal of RNA primers to form a continuous lagging strand, yet how mismatched primers introduced by error-prone primase are corrected remains unresolved. Here, we show that physiological levels of reactive oxygen species (ROS) initiate a redox-dependent mechanism that drives ADAR1-mediated adenosine-to-inosine (A-to-I) editing. Oxidation triggers ADAR1 dimerization at replication forks, enhancing RNA editing of mismatched primers—particularly those caused by ATP misincorporation on d(T+C)-rich centromeric DNA. This A-to-I editing step facilitates more efficient RNA primer degradation by RNase H2, thereby ensuring proper Okazaki fragment maturation. Disruption of ADAR1 oxidation results in increased unligated Okazaki fragments, single-stranded gaps and double-strand breaks, most prominently at centromeres. These findings reveal a role for ROS in safeguarding lagging-strand synthesis by coupling ADAR1 oxidation-induced A-to-I RNA editing to replication fork stability. Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.
Okazaki片段成熟需要有效地去除RNA引物以形成连续的滞后链，但如何纠正易出错引物引入的不匹配引物仍未解决。在这里，我们表明生理水平的活性氧（ROS）启动氧化还原依赖机制，驱动adar1介导的腺苷到肌苷（a -to-i）编辑。氧化触发复制叉上的ADAR1二聚化，增强错配引物的RNA编辑，特别是那些由富含d（T+C）的着丝粒DNA上ATP错误结合引起的引物。这一A-to-I编辑步骤有助于RNase H2更有效地降解RNA引物，从而确保适当的Okazaki片段成熟。ADAR1氧化的破坏导致未结扎的冈崎片段，单链间隙和双链断裂增加，最显著的是在着丝粒处。这些发现揭示了ROS通过将ADAR1氧化诱导的a -to- i RNA编辑与复制叉稳定性耦合，在保护滞后链合成方面的作用。
{"title":"Redox-driven ADAR1 activation promotes Okazaki fragment maturation and DNA replication integrity","authors":"Bin Chen, Guangchao Sun, Jake A. Kloeber, Huaping Xiao, Yaobin Ouyang, Fei Zhao, Ya Li, Shilin Xu, Sonja Dragojevic, Zheming Wu, Shouhai Zhu, Yiqun Han, Ping Yin, Xinyi Tu, Hongran Qin, Xiang Zhou, Kuntian Luo, Kevin L. Peterson, Jinzhou Huang, Taro Hitosugi, Haiming Dai, Min Deng, Robert W. Mutter, Zhenkun Lou","doi":"10.1038/s41594-025-01736-w","DOIUrl":"10.1038/s41594-025-01736-w","url":null,"abstract":"Okazaki fragment maturation requires efficient removal of RNA primers to form a continuous lagging strand, yet how mismatched primers introduced by error-prone primase are corrected remains unresolved. Here, we show that physiological levels of reactive oxygen species (ROS) initiate a redox-dependent mechanism that drives ADAR1-mediated adenosine-to-inosine (A-to-I) editing. Oxidation triggers ADAR1 dimerization at replication forks, enhancing RNA editing of mismatched primers—particularly those caused by ATP misincorporation on d(T+C)-rich centromeric DNA. This A-to-I editing step facilitates more efficient RNA primer degradation by RNase H2, thereby ensuring proper Okazaki fragment maturation. Disruption of ADAR1 oxidation results in increased unligated Okazaki fragments, single-stranded gaps and double-strand breaks, most prominently at centromeres. These findings reveal a role for ROS in safeguarding lagging-strand synthesis by coupling ADAR1 oxidation-induced A-to-I RNA editing to replication fork stability. Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"293-303"},"PeriodicalIF":10.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919892","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 : 2026-01-05DOI: 10.1038/s41594-025-01731-1
Kami Ahmad, Matt Wooten, Brittany N. Takushi, Velinda Vidaurre, Xin Chen, Steven Henikoff
In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3′ mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both Drosophila and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells. Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.
{"title":"Cell-cycle-dependent repression of histone gene transcription by histone H4","authors":"Kami Ahmad, Matt Wooten, Brittany N. Takushi, Velinda Vidaurre, Xin Chen, Steven Henikoff","doi":"10.1038/s41594-025-01731-1","DOIUrl":"10.1038/s41594-025-01731-1","url":null,"abstract":"In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3′ mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both Drosophila and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells. Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 1","pages":"145-156"},"PeriodicalIF":10.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01731-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1038/s41594-025-01733-z
Tommy O’Haren, Leila E. Rieder
The mechanisms that confine replication-dependent histone expression to S phase of the cell cycle remain unclear. Studies in Drosophila and cultured human cells show that non-nucleosomal histone H4 acts in a negative feedback loop to curtail histone gene expression at the end of S phase.
{"title":"A negative feedback mechanism controls histone gene expression","authors":"Tommy O’Haren, Leila E. Rieder","doi":"10.1038/s41594-025-01733-z","DOIUrl":"10.1038/s41594-025-01733-z","url":null,"abstract":"The mechanisms that confine replication-dependent histone expression to S phase of the cell cycle remain unclear. Studies in Drosophila and cultured human cells show that non-nucleosomal histone H4 acts in a negative feedback loop to curtail histone gene expression at the end of S phase.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 1","pages":"1-3"},"PeriodicalIF":10.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902692","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 : 2026-01-02DOI: 10.1038/s41594-025-01729-9
In this study, we applied single-particle cryogenic electron microscopy (cryo-EM) to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host-cell invasion. We assigned 40 distinct proteins to the cryo-EM densities and uncovered their spatial organization and interactions.
{"title":"High-resolution cryo-EM meets parasitology in structural models of the conoid from Toxoplasma","authors":"","doi":"10.1038/s41594-025-01729-9","DOIUrl":"10.1038/s41594-025-01729-9","url":null,"abstract":"In this study, we applied single-particle cryogenic electron microscopy (cryo-EM) to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host-cell invasion. We assigned 40 distinct proteins to the cryo-EM densities and uncovered their spatial organization and interactions.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 1","pages":"5-6"},"PeriodicalIF":10.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892958","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 : 2025-12-15DOI: 10.1038/s41594-025-01718-y
Alexandra G. Chivu, Brent A. Basso, Abderhman Abuhashem, Michelle M. Leger, Gilad Barshad, Edward J. Rice, Albert C. Vill, Wilfred Wong, Shao-Pei Chou, Gopal Chovatiya, Rebecca Brady, Jeramiah J. Smith, Athula H. Wikramanayake, César Arenas-Mena, Ilana L. Brito, Iñaki Ruiz-Trillo, Anna-Katerina Hadjantonakis, John T. Lis, James J. Lewis, Charles G. Danko
Promoter-proximal pausing of RNA polymerase (Pol) II is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here, we analyzed transcription in species across the tree of life. Unicellular eukaryotes display an accumulation of Pol II near transcription start sites, which we propose transitioned to the longer-lived, focused pause observed in metazoans. This transition coincided with the evolution of new subunits in the negative elongation factor (NELF) and 7SK complexes. Depletion of NELF in mammals shifted the promoter-proximal buildup of Pol II from the pause site into the early gene body and compromised transcriptional activation for a set of heat-shock genes. Our work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve. Here, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.
{"title":"Evolution of promoter-proximal pausing enabled a new layer of transcription control","authors":"Alexandra G. Chivu, Brent A. Basso, Abderhman Abuhashem, Michelle M. Leger, Gilad Barshad, Edward J. Rice, Albert C. Vill, Wilfred Wong, Shao-Pei Chou, Gopal Chovatiya, Rebecca Brady, Jeramiah J. Smith, Athula H. Wikramanayake, César Arenas-Mena, Ilana L. Brito, Iñaki Ruiz-Trillo, Anna-Katerina Hadjantonakis, John T. Lis, James J. Lewis, Charles G. Danko","doi":"10.1038/s41594-025-01718-y","DOIUrl":"10.1038/s41594-025-01718-y","url":null,"abstract":"Promoter-proximal pausing of RNA polymerase (Pol) II is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here, we analyzed transcription in species across the tree of life. Unicellular eukaryotes display an accumulation of Pol II near transcription start sites, which we propose transitioned to the longer-lived, focused pause observed in metazoans. This transition coincided with the evolution of new subunits in the negative elongation factor (NELF) and 7SK complexes. Depletion of NELF in mammals shifted the promoter-proximal buildup of Pol II from the pause site into the early gene body and compromised transcriptional activation for a set of heat-shock genes. Our work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve. Here, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"282-292"},"PeriodicalIF":10.1,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759744","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}
{"title":"Closing 2025, and a look ahead","authors":"","doi":"10.1038/s41594-025-01732-0","DOIUrl":"10.1038/s41594-025-01732-0","url":null,"abstract":"We review 2025 and discuss some of the foremost initiatives developed at the journal. We also look back at discoveries we have been proud to publish.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2373-2373"},"PeriodicalIF":10.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01732-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1038/s41594-025-01725-z
Ifigenia Tsitsa, Anja Conev, Alessia David, Suhail A. Islam, Michael J. E. Sternberg
The AlphaFold database, released in 2022, modeled UniProt sequences from April 2021 and now provides 200 million predicted protein structures. Of the 20,504 full-length predicted human structures, 631 entries conflict with the June 2025 UniProt release. Similar conflicts across species highlight how bioinformatics resources can rapidly age.
{"title":"The aging of the AlphaFold database","authors":"Ifigenia Tsitsa, Anja Conev, Alessia David, Suhail A. Islam, Michael J. E. Sternberg","doi":"10.1038/s41594-025-01725-z","DOIUrl":"10.1038/s41594-025-01725-z","url":null,"abstract":"The AlphaFold database, released in 2022, modeled UniProt sequences from April 2021 and now provides 200 million predicted protein structures. Of the 20,504 full-length predicted human structures, 631 entries conflict with the June 2025 UniProt release. Similar conflicts across species highlight how bioinformatics resources can rapidly age.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2374-2376"},"PeriodicalIF":10.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717909","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}
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