Cell Research最新文献_第8页

Orchestrating NTSR1 signaling from the interface 编排来自接口的NTSR1信令

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-21 DOI: 10.1038/s41422-025-01121-8

Xianglin Huang, Brian E. Krumm, Bryan L. Roth

引用次数: 0

Spliceosome-associated quality control 剪接体相关质量控制

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-21 DOI: 10.1038/s41422-025-01118-3

Nikita Sharaev, Jiangfeng Zhao, Wojciech P. Galej

引用次数: 0

Pyrimidine synthase CAD deamidates and inactivates p53 嘧啶合酶CAD使p53脱酰胺并失活。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-17 DOI: 10.1038/s41422-025-01112-9

Yue Qi, Zizheng Tan, Hanyu Chen, Ziqi Xiao, Liang Zhang, Boxuan Wu, Chennan Liu, Yunqian Gao, Xueyan Yang, Lingqian Wu, Lei Lu, Hongyan Wang

引用次数: 0

Author Correction: Structural and functional evidence that GPR30 is not a direct estrogen receptor 作者更正：结构和功能证据表明GPR30不是直接雌激素受体。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-16 DOI: 10.1038/s41422-025-01113-8

Heng Liu, Shimeng Guo, Antao Dai, Peiyu Xu, Xin Li, Sijie Huang, Xinheng He, Kai Wu, Xinyue Zhang, Dehua Yang, Xin Xie, H. Eric Xu

引用次数: 0

Mechanistic insights into RNA cleavage by human Argonaute2–siRNA complex 人类Argonaute2-siRNA复合物裂解RNA的机制

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-16 DOI: 10.1038/s41422-025-01114-7

Zhenzhen Li, Qikui Xu, Yan Zhang, Jing Zhong, Tianxiang Zhang, Junchao Xue, Shuxian Liu, Haishan Gao, Z. Z. Zhao Zhang, Jianping Wu, En-Zhi Shen

{"title":"Mechanistic insights into RNA cleavage by human Argonaute2–siRNA complex","authors":"Zhenzhen Li, Qikui Xu, Yan Zhang, Jing Zhong, Tianxiang Zhang, Junchao Xue, Shuxian Liu, Haishan Gao, Z. Z. Zhao Zhang, Jianping Wu, En-Zhi Shen","doi":"10.1038/s41422-025-01114-7","DOIUrl":"10.1038/s41422-025-01114-7","url":null,"abstract":"In animals, AGO-clade Argonaute proteins utilize small interfering RNAs (siRNAs) as guides to recognize target with complete complementarity, resulting in target RNA cleavage that is a critical step for target silencing. These proteins feature a constricted nucleic acid-binding channel that limits base pairing between the guide and target beyond the seed region. How the AGO–siRNA complexes overcome this structural limitation and achieve efficient target cleavage remains unclear. We performed cryo-electron microscopy of human AGO–siRNA complexes bound to target RNAs of increasing lengths to examine the conformational changes associated with target recognition and cleavage. Initially, conformational transition propagates from the opening of the PAZ domain and extends through a repositioning of the PIWI–L1–N domain toward the binding channel, facilitating the capture of siRNA–target duplex. Subsequent extension of base pairing drives the downward movement of the PIWI–L1–N domain to enable catalytic activation. Finally, further base pairing toward the 3′ end of siRNA destabilizes the PAZ–N domain, resulting in a “uni-lobed” architecture, which might facilitate the multi-turnover action of the AGO–siRNA enzyme complex. In contrast to PIWI-clade Argonautes, the “uni-lobed” structure of the AGO complex makes multiple contacts with the target in the central region of the siRNA–target duplex, positioning it within the catalytic site. Our findings shed light on the stepwise mechanisms by which the AGO–siRNA complex executes target RNA cleavage and offer insights into the distinct operational modalities of AGO and PIWI proteins in achieving such cleavage.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"453-464"},"PeriodicalIF":25.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836746","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

Why resident microglial-like cells were missed in the peripheral nervous system. 为什么周围神经系统中缺少常驻小胶质样细胞。

IF 28.1 1区生物学

Cell Research Pub Date : 2025-04-15 DOI: 10.1038/s41422-025-01119-2

Michal Schwartz

引用次数: 0

Beyond peptide targeting sequences: machine learning of cellular condensate localization 超越肽靶向序列：细胞凝聚物定位的机器学习

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-14 DOI: 10.1038/s41422-025-01115-6

Jonathon A. Ditlev, Julie D. Forman-Kay

引用次数: 0

Selective CDK4 inhibition holds promise for breast cancer 选择性CDK4抑制有望治疗乳腺癌

IF 44.1 1区生物学

Cell Research Pub Date : 2025-04-14 DOI: 10.1038/s41422-025-01117-4

Manuel Beltrán-Visiedo, Rebecca M. Shulman, Lorenzo Galluzzi

引用次数: 0

Phase separation paints Xi with Xist 相分离把Xi和Xist画在一起

IF 25.9 1区生物学

Cell Research Pub Date : 2025-04-14 DOI: 10.1038/s41422-025-01116-5

Thomas C. T. Michaels, Anton Wutz

引用次数: 0

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 25.9 1区生物学

Cell Research Pub 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":"35 6","pages":"423-436"},"PeriodicalIF":25.9,"publicationDate":"2025-04-11","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