Cell Research最新文献_第3页

Structural basis of stepwise proton sensing-mediated GPCR activation. 质子感应介导的GPCR逐步激活的结构基础。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1038/s41422-025-01092-w

Xiaolei Yue, Li Peng, Shenhui Liu, Bingjie Zhang, Xiaodan Zhang, Hao Chang, Yuan Pei, Xiaoting Li, Junlin Liu, Wenqing Shui, Lijie Wu, Huji Xu, Zhi-Jie Liu, Tian Hua

{"title":"Structural basis of stepwise proton sensing-mediated GPCR activation.","authors":"Xiaolei Yue, Li Peng, Shenhui Liu, Bingjie Zhang, Xiaodan Zhang, Hao Chang, Yuan Pei, Xiaoting Li, Junlin Liu, Wenqing Shui, Lijie Wu, Huji Xu, Zhi-Jie Liu, Tian Hua","doi":"10.1038/s41422-025-01092-w","DOIUrl":"10.1038/s41422-025-01092-w","url":null,"abstract":"The regulation of pH homeostasis is crucial in many biological processes vital for survival, growth, and function of life. The pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 and GPR68, play a pivotal role in detecting changes in extracellular proton concentrations, impacting both physiological and pathological states. However, comprehensive understanding of the proton sensing mechanism is still elusive. Here, we determined the cryo-electron microscopy structures of GPR4 and GPR65 in various activation states across different pH levels, coupled with Gs, Gq or G13 proteins, as well as a small molecule NE52-QQ57-bound inactive GPR4 structure. These structures reveal the dynamic nature of the extracellular loop 2 and its signature conformations in different receptor states, and disclose the proton sensing mechanism mediated by networks of extracellular histidine and carboxylic acid residues. Notably, we unexpectedly captured partially active intermediate states of both GPR4-Gs and GPR4-Gq complexes, and identified a unique allosteric binding site for NE52-QQ57 in GPR4. By integrating prior investigations with our structural analysis and mutagenesis data, we propose a detailed atomic model for stepwise proton sensation and GPCR activation. These insights may pave the way for the development of selective ligands and targeted therapeutic interventions for pH sensing-relevant diseases.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":"423-436"},"PeriodicalIF":28.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979144","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}

引用次数: 0

Mechanisms of chromatin remodeling by the human Snf2-type ATPase SNF2H. 人类snf2型atp酶SNF2H的染色质重塑机制。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-06-01 Epub Date: 2025-04-03 DOI: 10.1038/s41422-025-01103-w

Deepshikha Malik, Ashish Deshmukh, Silvija Bilokapic, Mario Halic

引用次数: 0

FUSTer than stress granules: a prion-like domain warns plants of heat 比压力颗粒更严重：一个类似朊病毒的区域警告植物热

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-29 DOI: 10.1038/s41422-025-01133-4

Panagiotis N. Moschou, Peter V. Bozhkov

引用次数: 0

Editorial Expression of Concern: p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity. 编辑关注：p53的线粒体易位和MOMP作用独立于Puma和Bax，严重破坏线粒体膜的完整性。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-05-29 DOI: 10.1038/s41422-025-01129-0

Sonja Wolff, Susan Erster, Gustavo Palacios, Ute M Moll

引用次数: 0

Filament assembly powers NbaSPARDA in bacterial defense 纤维组装为NbaSPARDA的细菌防御提供动力

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-19 DOI: 10.1038/s41422-025-01131-6

Beibei Wang, Qiunan Jin, Hui Yang

引用次数: 0

Targeting an alternative route: autophagy in RAS-driven cancers. 靶向另一种途径：ras驱动癌症的自噬。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-16 DOI: 10.1038/s41422-025-01127-2

Alina Üffing,Eleanor Attridge,Sharon A Tooze

引用次数: 0

Mucin-like protein of Crimean-Congo hemorrhagic fever virus is a key virulence factor and a potent target for developing novel attenuated vaccine. 克里米亚-刚果出血热病毒黏蛋白样蛋白是一种重要的毒力因子，是研制新型减毒疫苗的有力靶点。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-16 DOI: 10.1038/s41422-025-01130-7

Liushuai Li,Yajie Liu,Juhong Rao,Hengrui Hu,Jia Liu,Xi Wang,Jiang Li,Zhihong Hu,Manli Wang

引用次数: 0

A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis. 在拟南芥中，一个热传感器FUST1通过生物分子凝聚启动热诱导应激颗粒的形成。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-14 DOI: 10.1038/s41422-025-01125-4

Pan Geng,Changxuan Li,Xuebo Quan,Jiaxuan Peng,Zhiying Yao,Yunhe Wang,Ming Yang,Yanning Wang,Yunfan Jin,Yan Xiong,Hongtao Liu,Yijun Qi,Peiguo Yang,Kai Huang,Xiaofeng Fang

{"title":"A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis.","authors":"Pan Geng,Changxuan Li,Xuebo Quan,Jiaxuan Peng,Zhiying Yao,Yunhe Wang,Ming Yang,Yanning Wang,Yunfan Jin,Yan Xiong,Hongtao Liu,Yijun Qi,Peiguo Yang,Kai Huang,Xiaofeng Fang","doi":"10.1038/s41422-025-01125-4","DOIUrl":"https://doi.org/10.1038/s41422-025-01125-4","url":null,"abstract":"The ability to sense cellular temperature and induce physiological changes is pivotal for plants to cope with warming climate. Biomolecular condensation is emerging as a thermo-sensing mechanism, but the underlying molecular basis remains elusive. Here we show that an intrinsically disordered protein FUST1 senses heat via its condensation in Arabidopsis thaliana. Heat-dependent condensation of FUST1 is primarily determined by its prion-like domain (PrLD). All-atom molecular dynamics simulation and experimental validation reveal that PrLD encodes a thermo-switch, experiencing lock-to-open conformational changes that control the intermolecular contacts. FUST1 interacts with integral stress granule (SG) components and localizes in the SGs. Importantly, FUST1 condensation is autonomous and precedes condensation of several known SG markers and is indispensable for SG assembly. Loss of FUST1 significantly delays SG assembly and impairs both basal and acquired heat tolerance. These findings illuminate the molecular basis for thermo-sensing by biomolecular condensation and shed light on the molecular mechanism of heat stress granule assembly.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"2 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945476","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}

引用次数: 0

DNA remnants in red blood cells enable early detection of cancer 红细胞中的DNA残余物有助于早期发现癌症

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-09 DOI: 10.1038/s41422-025-01122-7

Haobo Sun, Xingyun Yao, Yurong Jiao, Xiangxing Kong, Yuehua Han, Ying Li, Jianping Ge, Yanfei Cao, Hongsheng Lu, Pingli Wang, Yu Xu, Jun Li, Kefeng Ding, Xiaofei Gao

{"title":"DNA remnants in red blood cells enable early detection of cancer","authors":"Haobo Sun, Xingyun Yao, Yurong Jiao, Xiangxing Kong, Yuehua Han, Ying Li, Jianping Ge, Yanfei Cao, Hongsheng Lu, Pingli Wang, Yu Xu, Jun Li, Kefeng Ding, Xiaofei Gao","doi":"10.1038/s41422-025-01122-7","DOIUrl":"https://doi.org/10.1038/s41422-025-01122-7","url":null,"abstract":"Cytoplasmic DNA emerges as a consequence of genomic instability. However, its potential role in disease diagnosis has yet to be fully explored. Here we analyzed DNA remnants in mature red blood cells (rbcDNA) from both healthy individuals and cancer patients. Our study unveiled distinct genomic profiles in rbcDNA from cancer patients with early-stage solid tumors compared to those of healthy donors. Significant changes in read counts at specific genomic regions within rbcDNA were identified in patients, which were termed tumor-associated rbcDNA features. These features demonstrated potential for highly accurate early-stage cancer detection, proposing a novel approach for cancer detection. Moreover, tumor-associated rbcDNA features were observed in tumor mouse models, with some features being conserved between mice and humans. Chronic, but not transient, up-regulation of interleukin-18 is essential for the development of these features by promoting DNA damage in bone marrow hematopoietic cells through the up-regulation of NR4A1. These results underscore the remote regulation of chromosomal stability in hematopoietic cells by solid tumors and propose tumor-associated rbcDNA features as a promising strategy for early cancer detection.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"110 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926856","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}

引用次数: 0

Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus 异体抗cd19 CAR-T细胞诱导难治性系统性红斑狼疮缓解

IF 44.1 1区生物学

Cell Research Pub Date : 2025-05-08 DOI: 10.1038/s41422-025-01128-1

Chunmei Yang, Chuanyin Sun, Binghe Tan, Chao Hu, Liyan Wan, Chris Wang, Xiujuan Shi, Juliang Qin, Na Zhang, Biao Zheng, Mingyao Liu, Jin Lin, Bing Du, Hongyan Tong

引用次数: 0