Nature Communications最新文献_第9页

Structural insights into the dual Ca2+-sensor-mediated activation of the PPEF phosphatase family

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58261-z

Jia Liu, Cang Wu, Yuyang Liu, Qiangou Chen, Yuzhen Ding, Zhiqiao Lin, Lifeng Pan, Kang Xiao, Jianchao Li, Zhongmin Liu, Wei Liu

{"title":"Structural insights into the dual Ca2+-sensor-mediated activation of the PPEF phosphatase family","authors":"Jia Liu, Cang Wu, Yuyang Liu, Qiangou Chen, Yuzhen Ding, Zhiqiao Lin, Lifeng Pan, Kang Xiao, Jianchao Li, Zhongmin Liu, Wei Liu","doi":"10.1038/s41467-025-58261-z","DOIUrl":"https://doi.org/10.1038/s41467-025-58261-z","url":null,"abstract":"Serine/threonine-protein phosphatases with EF-hands (PPEFs) are a family of highly conserved proteins implicated in cancer and neuronal degeneration. The initially characterized member, Drosophila melanogaster retinal degeneration C (RDGC) contains a calmodulin (CaM)-interacting extended-IQ motif and a Ca2+-binding EF-like/EF-hand tandem. However, the molecular regulation of PPEF is poorly understood. In this study, we use cryogenic-electron microscopy to delineate the structures of the RDGC/CaM holoenzyme. In the absence of Ca2+, CaM and the EF-like/EF-hand tandem allow the extended-IQ motif to block substrate access to the catalytic sites, constituting an auto-inhibitory mechanism. Upon Ca2+ binding, CaM and the EF-like/EF-hand tandem drive drastic conformational changes in the extended-IQ motif to unlock the catalytic sites. This dual Ca2+-sensor-mediated activation is evolutionarily conserved in mammals. This study provides mechanistic insight into the molecular activation of PPEFs, paving the way for the development of therapeutic strategies for PPEF-related human diseases.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"216 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745572","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}

引用次数: 0

Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58180-z

Yuanyuan Qu, Wanbo Tai, Enhao Ma, Qiwei Jiang, Miao Fan, Wangcheng Xiao, Chongyu Tian, Yang Liu, Jianying Liu, Xinquan Wang, Jiwan Ge, Gong Cheng

{"title":"Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus","authors":"Yuanyuan Qu, Wanbo Tai, Enhao Ma, Qiwei Jiang, Miao Fan, Wangcheng Xiao, Chongyu Tian, Yang Liu, Jianying Liu, Xinquan Wang, Jiwan Ge, Gong Cheng","doi":"10.1038/s41467-025-58180-z","DOIUrl":"https://doi.org/10.1038/s41467-025-58180-z","url":null,"abstract":"The global outbreak of monkeypox virus (MPXV), combined with the termination of smallpox vaccination and the lack of specific antiviral treatments, raises increasing concerns. The surface proteins M1R and B6R of MPXV are crucial for virus transmission and serve as key targets for vaccine development. In this study, a panel of human antibodies targeting M1R and B6R is isolated from a human antibody library using phage display technology. Among these antibodies, A138 against M1R and B026 against B6R show the most potent broad-spectrum neutralizing activities against MPXV and Vaccinia virus (VACV). When used in combination, A138 and B026 exhibit complementary neutralizing activity against both viruses in vitro. X-ray crystallography reveales that A138 binds to the loop regions of M1R, similar to the vulnerable epitope of 7D11 on VACV L1R. By contrast, A129 targets a more cryptic epitope, primarily comprising the β-strands of M1R. Moreover, prophylactic and therapeutic administration of A138 or B026 alone provides partial protection, while combining these two antibodies results in enhanced protection against VACV in male C57BL/6 mice. This study demonstrates of a dual-targeting strategy using two different components of the virion for the prevention and treatment of MPXV infection.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"133 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745728","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}

引用次数: 0

Transcriptomic and spatial GABAergic neuron subtypes in zona incerta mediate distinct innate behaviors

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-57896-2

Mengyue Zhu, Jieqiao Peng, Mi Wang, Shan Lin, Huiying Zhang, Yu Zhou, Xinyue Dai, Huiying Zhao, Yan-qin Yu, Li Shen, Xiao-Ming Li, Jiadong Chen

{"title":"Transcriptomic and spatial GABAergic neuron subtypes in zona incerta mediate distinct innate behaviors","authors":"Mengyue Zhu, Jieqiao Peng, Mi Wang, Shan Lin, Huiying Zhang, Yu Zhou, Xinyue Dai, Huiying Zhao, Yan-qin Yu, Li Shen, Xiao-Ming Li, Jiadong Chen","doi":"10.1038/s41467-025-57896-2","DOIUrl":"https://doi.org/10.1038/s41467-025-57896-2","url":null,"abstract":"Understanding the anatomical connection and behaviors of transcriptomic neuron subtypes is critical to delineating cell type-specific functions in the brain. Here we integrated single-nucleus transcriptomic sequencing, in vivo circuit mapping, optogenetic and chemogenetic approaches to dissect the molecular identity and function of heterogeneous GABAergic neuron populations in the zona incerta (ZI) in mice, a region involved in modulating various behaviors. By microdissecting ZI for transcriptomic and spatial gene expression analyses, our results revealed two non-overlapping Ecel1- and Pde11a-expressing GABAergic neurons with dominant expression in the rostral and medial zona incerta (ZIrEcel1 and ZImPde11a), respectively. The GABAergic projection from ZIrEcel1 to periaqueductal gray mediates self-grooming, while the GABAergic projection from ZImPde11a to the oral part of pontine reticular formation promotes transition from sleep to wakefulness. Together, our results revealed the molecular markers, spatial organization and specific neuronal circuits of two discrete GABAergic projection neuron populations in segregated subregions of the ZI that mediate distinct innate behaviors, advancing our understanding of the functional organization of the brain.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"32 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745743","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}

引用次数: 0

Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58447-5

Wenkai Wang, Zhuo Cheng, Miao Yu, Ke Liu, Hongli Duan, Yang Zhang, Xinle Huang, Menghuan Li, Changqing Li, Yan Hu, Zhong Luo, Minghan Liu

{"title":"Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes","authors":"Wenkai Wang, Zhuo Cheng, Miao Yu, Ke Liu, Hongli Duan, Yang Zhang, Xinle Huang, Menghuan Li, Changqing Li, Yan Hu, Zhong Luo, Minghan Liu","doi":"10.1038/s41467-025-58447-5","DOIUrl":"https://doi.org/10.1038/s41467-025-58447-5","url":null,"abstract":"Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745316","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}

引用次数: 0

Molecular basis for the calcium-dependent activation of the ribonuclease EndoU

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58462-6

Florian Malard, Kristen Dias, Margaux Baudy, Stéphane Thore, Brune Vialet, Philippe Barthélémy, Sébastien Fribourg, Fedor V. Karginov, Sébastien Campagne

{"title":"Molecular basis for the calcium-dependent activation of the ribonuclease EndoU","authors":"Florian Malard, Kristen Dias, Margaux Baudy, Stéphane Thore, Brune Vialet, Philippe Barthélémy, Sébastien Fribourg, Fedor V. Karginov, Sébastien Campagne","doi":"10.1038/s41467-025-58462-6","DOIUrl":"https://doi.org/10.1038/s41467-025-58462-6","url":null,"abstract":"Ribonucleases (RNases) are ubiquitous enzymes that process or degrade RNA, essential for cellular functions and immune responses. The EndoU-like superfamily includes endoribonucleases conserved across bacteria, eukaryotes, and certain viruses, with an ancient evolutionary link to the ribonuclease A-like superfamily. Both bacterial EndoU and animal RNase A share a similar fold and function independently of cofactors. In contrast, the eukaryotic EndoU catalytic domain requires divalent metal ions for catalysis, possibly due to an N-terminal extension near the catalytic core. In this study, we use biophysical and computational techniques along with in vitro assays to investigate the calcium-dependent activation of human EndoU. We determine the crystal structure of EndoU bound to calcium and find that calcium binding remote from the catalytic triad triggers water-mediated intramolecular signaling and structural changes, activating the enzyme through allostery. Calcium binding involves residues from both the catalytic core and the N-terminal extension, indicating that the N-terminal extension interacts with the catalytic core to modulate activity in response to calcium. Our findings suggest that similar mechanisms may be present across all eukaryotic EndoUs, highlighting a unique evolutionary adaptation that connects endoribonuclease activity to cellular signaling in eukaryotes.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"89 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745752","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}

引用次数: 0

A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-57077-1

Anton Safonov, Tomoki T. Nomakuchi, Elizabeth Chao, Carrie Horton, Jill S. Dolinsky, Amal Yussuf, Marcy Richardson, Virginia Speare, Shuwei Li, Zoe C. Bogus, Maria Bonanni, Anna Raper, Trust Odia, Bradley S. Wubbenhorst, Elsa Faulders, Elisabeth M. Schuth, Kate Loranger, Jingwen Zhang, Carly Bess Scalise, Adam ElNaggar, Youbao Sha, Stephanie A. Felker, Jeffrey Weitzel, Staci Kallish, Marylyn D. Ritchie, Katherine L. Nathanson, Theodore G. Drivas

{"title":"A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations","authors":"Anton Safonov, Tomoki T. Nomakuchi, Elizabeth Chao, Carrie Horton, Jill S. Dolinsky, Amal Yussuf, Marcy Richardson, Virginia Speare, Shuwei Li, Zoe C. Bogus, Maria Bonanni, Anna Raper, Trust Odia, Bradley S. Wubbenhorst, Elsa Faulders, Elisabeth M. Schuth, Kate Loranger, Jingwen Zhang, Carly Bess Scalise, Adam ElNaggar, Youbao Sha, Stephanie A. Felker, Jeffrey Weitzel, Staci Kallish, Marylyn D. Ritchie, Katherine L. Nathanson, Theodore G. Drivas","doi":"10.1038/s41467-025-57077-1","DOIUrl":"https://doi.org/10.1038/s41467-025-57077-1","url":null,"abstract":"Loss of function variants in the NF1 gene cause neurofibromatosis type 1, a genetic disorder characterized by complete penetrance, characteristic physical exam findings, and a substantially increased risk for malignancy. However, our understanding of the disorder is based on patients ascertained through phenotype-first approaches, which estimate prevalence at 1 in 3000. Leveraging a genotype-first approach in multiple large patient cohorts including over one million individuals, we demonstrate an unexpectedly high prevalence (1 in 1,286) of NF1 pathogenic variants. Half are identified in individuals lacking clinical features of NF1, with many appearing to have post-zygotic mosaicism for the identified variant. Incidentally discovered variants are not associated with classic neurofibromatosis features but are associated with an increased incidence of malignancy compared to control populations. Our findings suggest that NF1 pathogenic variants are substantially more common than previously thought, often characterized by somatic mosaicism and reduced penetrance, and are important contributors to cancer risk in the general population.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"38 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745757","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}

引用次数: 0

Analysis of allohexaploid wheatgrass genome reveals its Y haplome origin in Triticeae and high-altitude adaptation 异源六倍体小麦草基因组分析揭示了其在三尖杉科中的 Y 单倍体起源和高海拔适应性

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58341-0

Yi Xiong, Shuai Yuan, Yanli Xiong, Lizuiyue Li, Jinghan Peng, Jin Zhang, Xing Fan, Chengzhi Jiang, Li-na Sha, Zhaoting Wang, Xue Peng, Zecheng Zhang, Qingqing Yu, Xiong Lei, Zhixiao Dong, Yingjie Liu, Junming Zhao, Guangrong Li, Zujun Yang, Shangang Jia, Daxu Li, Ming Sun, Shiqie Bai, Jianquan Liu, Yongzhi Yang, Xiao Ma

{"title":"Analysis of allohexaploid wheatgrass genome reveals its Y haplome origin in Triticeae and high-altitude adaptation","authors":"Yi Xiong, Shuai Yuan, Yanli Xiong, Lizuiyue Li, Jinghan Peng, Jin Zhang, Xing Fan, Chengzhi Jiang, Li-na Sha, Zhaoting Wang, Xue Peng, Zecheng Zhang, Qingqing Yu, Xiong Lei, Zhixiao Dong, Yingjie Liu, Junming Zhao, Guangrong Li, Zujun Yang, Shangang Jia, Daxu Li, Ming Sun, Shiqie Bai, Jianquan Liu, Yongzhi Yang, Xiao Ma","doi":"10.1038/s41467-025-58341-0","DOIUrl":"https://doi.org/10.1038/s41467-025-58341-0","url":null,"abstract":"Phylogenetic origin of the Y haplome present in allopolyploid Triticeae species remains unknown. Here, we report the 10.47 Gb chromosome-scale genome of allohexaploid Elymus nutans (StStYYHH). Phylogenomic analyses reveal that the Y haplome is sister to the clade comprising V and Jv haplomes from Dasypyrum and Thinopyum. In addition, H haplome from the Hordeum-like ancestor, St haplome from the Pseudoroegneria-like ancestor and Y haplome are placed in the successively diverged clades. Resequencing data reveal the allopolyploid origins with St, Y, and H haplome combinations in Elymus. Population genomic analyses indicate that E. nutans has expanded from medium to high/low-altitude regions. Phenotype/environmental association analyses identify MAPKKK18 promoter mutations reducing its expression, aiding UV-B adaptation in high-altitude populations. These findings enhance understanding of allopolyploid evolution and aid in breeding forage and cereal crops through intergeneric hybridization within Triticeae.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"12 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745590","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}

引用次数: 0

AI-based detection and classification of anomalous aortic origin of coronary arteries using coronary CT angiography images

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58362-9

Isaac Shiri, Giovanni Baj, Pooya Mohammadi Kazaj, Marius R. Bigler, Anselm W. Stark, Waldo Valenzuela, Ryota Kakizaki, Matthias Siepe, Stephan Windecker, Lorenz Räber, Andreas A. Giannopoulos, George CM. Siontis, Ronny R. Buechel, Christoph Gräni

{"title":"AI-based detection and classification of anomalous aortic origin of coronary arteries using coronary CT angiography images","authors":"Isaac Shiri, Giovanni Baj, Pooya Mohammadi Kazaj, Marius R. Bigler, Anselm W. Stark, Waldo Valenzuela, Ryota Kakizaki, Matthias Siepe, Stephan Windecker, Lorenz Räber, Andreas A. Giannopoulos, George CM. Siontis, Ronny R. Buechel, Christoph Gräni","doi":"10.1038/s41467-025-58362-9","DOIUrl":"https://doi.org/10.1038/s41467-025-58362-9","url":null,"abstract":"Anomalous aortic origin of the coronary artery (AAOCA) is a rare cardiac condition that can lead to ischemia or sudden cardiac death, yet it is often overlooked or falsely classified in routine coronary CT angiography (CCTA). Here, we developed, validated, externally tested, and clinically evaluated a fully automated artificial intelligence (AI)-based tool for detecting and classifying AAOCA in 3D-CCTA images. The discriminatory performance of the different models achieved an AUC ≥ 0.99, with sensitivity and specificity ranging 0.95-0.99 across all internal and external testing datasets. Here, we present an AI-based model that enables fully automated and accurate detection and classification of AAOCA, with the potential for seamless integration into clinical workflows. The tool can deliver real-time alerts for potentially high-risk AAOCA anatomies, while also enabling the analysis of large 3D-CCTA cohorts. This will support a deeper understanding of the risks associated with this rare condition and contribute to improving its future management.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"33 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745595","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}

引用次数: 0

Dynamic coding and sequential integration of multiple reward attributes by primate amygdala neurons 灵长类杏仁核神经元对多种奖励属性的动态编码和顺序整合

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58270-y

Fabian Grabenhorst, Raymundo Báez-Mendoza

{"title":"Dynamic coding and sequential integration of multiple reward attributes by primate amygdala neurons","authors":"Fabian Grabenhorst, Raymundo Báez-Mendoza","doi":"10.1038/s41467-025-58270-y","DOIUrl":"https://doi.org/10.1038/s41467-025-58270-y","url":null,"abstract":"The value of visual stimuli guides learning, decision-making, and motivation. Although stimulus values often depend on multiple attributes, how neurons extract and integrate distinct value components from separate cues remains unclear. Here we recorded the activity of amygdala neurons while two male monkeys viewed sequential cues indicating the probability and magnitude of expected rewards. Amygdala neurons frequently signaled reward probability in an abstract, stimulus-independent code that generalized across cue formats. While some probability-coding neurons were insensitive to magnitude information, signaling ‘pure’ probability rather than value, many neurons showed biphasic responses that signaled probability and magnitude in a dynamic (temporally-patterned) and flexible (reversible) value code. Specific amygdala neurons integrated these reward attributes into risk signals that quantified the variance of expected rewards, distinct from value. Population codes were accurate, mutually transferable between value components, and expressed differently across amygdala nuclei. Our findings identify amygdala neurons as a substrate for the sequential integration of multiple reward attributes into value and risk.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745592","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}

引用次数: 0

Structural basis for allosteric modulation of M. tuberculosis proteasome core particle

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-04-01 DOI: 10.1038/s41467-025-58430-0

Madison Turner, Adwaith B. Uday, Algirdas Velyvis, Enrico Rennella, Natalie Zeytuni, Siavash Vahidi

{"title":"Structural basis for allosteric modulation of M. tuberculosis proteasome core particle","authors":"Madison Turner, Adwaith B. Uday, Algirdas Velyvis, Enrico Rennella, Natalie Zeytuni, Siavash Vahidi","doi":"10.1038/s41467-025-58430-0","DOIUrl":"https://doi.org/10.1038/s41467-025-58430-0","url":null,"abstract":"The Mycobacterium tuberculosis (Mtb) proteasome system selectively degrades damaged or misfolded proteins and is crucial for the pathogen’s survival within the host. Targeting the 20S core particle (CP) offers a viable strategy for developing tuberculosis treatments. The activity of Mtb 20S CP, like that of its eukaryotic counterpart, is allosterically regulated, yet the specific conformations involved have not been captured in high-resolution structures to date. Here, we use single-particle electron cryomicroscopy and H/D exchange mass spectrometry to determine the Mtb 20S CP structure in an auto-inhibited state that is distinguished from the canonical resting state by the conformation of switch helices at the α/β interface. The rearrangement of these helices collapses the S1 pocket, effectively inhibiting substrate binding. Biochemical experiments show that the Mtb 20S CP activity can be altered through allosteric sites far from the active site. Our findings underscore the potential of targeting allostery to develop antituberculosis therapeutics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"183 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758660","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}

引用次数: 0