Cell Discovery最新文献_第3页

Structural insights into human ABCD3-mediated peroxisomal acyl-CoA translocation. 人类 ABCD3 介导的过氧物酶体酰基-CoA 转运的结构性启示。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-09-03 DOI: 10.1038/s41421-024-00722-8

Yang Li, Zhi-Peng Chen, Da Xu, Liang Wang, Meng-Ting Cheng, Cong-Zhao Zhou, Yuxing Chen, Wen-Tao Hou

{"title":"Structural insights into human ABCD3-mediated peroxisomal acyl-CoA translocation.","authors":"Yang Li, Zhi-Peng Chen, Da Xu, Liang Wang, Meng-Ting Cheng, Cong-Zhao Zhou, Yuxing Chen, Wen-Tao Hou","doi":"10.1038/s41421-024-00722-8","DOIUrl":"10.1038/s41421-024-00722-8","url":null,"abstract":"Human ABC transporters ABCD1-3 are all localized on the peroxisomal membrane and participate in the β-oxidation of fatty acyl-CoAs, but they differ from each other in substrate specificity. The transport of branched-chain fatty acids from cytosol to peroxisome is specifically driven by ABCD3, dysfunction of which causes severe liver diseases such as hepatosplenomegaly. Here we report two cryogenic electron microscopy (cryo-EM) structures of ABCD3 bound to phytanoyl-CoA and ATP at resolutions of 2.9 Å and 3.2 Å, respectively. A pair of phytanoyl-CoA molecules were observed in ABCD3, each binding to one transmembrane domain (TMD), which is distinct from our previously reported structure of ABCD1, where each fatty acyl-CoA molecule strongly crosslinks two TMDs. Upon ATP binding, ABCD3 exhibits a conformation that is open towards the peroxisomal matrix, leaving two extra densities corresponding to two CoA molecules deeply embedded in the translocation cavity. Structural analysis combined with substrate-stimulated ATPase activity assays indicated that the present structures might represent two states of ABCD3 in the transport cycle. These findings advance our understanding of fatty acid oxidation and the molecular pathology of related diseases.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119104","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

Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor. 催乳素释放肽通过其 G 蛋白偶联受体识别和传递信号的分子机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-09-03 DOI: 10.1038/s41421-024-00724-6

Yang Li, Qingning Yuan, Xinheng He, Yumu Zhang, Chongzhao You, Canrong Wu, Jingru Li, H Eric Xu, Li-Hua Zhao

{"title":"Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.","authors":"Yang Li, Qingning Yuan, Xinheng He, Yumu Zhang, Chongzhao You, Canrong Wu, Jingru Li, H Eric Xu, Li-Hua Zhao","doi":"10.1038/s41421-024-00724-6","DOIUrl":"10.1038/s41421-024-00724-6","url":null,"abstract":"Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide-receptor system.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119102","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

PCaseek: ultraspecific urinary tumor DNA detection using deep learning for prostate cancer diagnosis and Gleason grading. PCaseek：利用深度学习进行超特异性尿液肿瘤 DNA 检测，用于前列腺癌诊断和格里森分级。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-09-03 DOI: 10.1038/s41421-024-00710-y

Gaojie Li, Ye Wang, Ying Wang, Baojun Wang, Yuan Liang, Ping Wang, Yudan He, Xiaoshan Hu, Guojun Liu, Zhentao Lei, Bao Zhang, Yue Shi, Xu Gao, Xu Zhang, Weimin Ci

引用次数: 0

Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis. 肠道微生物群衍生的吲哚-3-乙酸通过促进 I 型胶原蛋白的合成抑制高度近视的发展。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-27 DOI: 10.1038/s41421-024-00709-5

Hao Li, Yu Du, Kaiwen Cheng, Yuxi Chen, Ling Wei, Yujun Pei, Xiaoyu Wang, Lan Wang, Ye Zhang, Xiaoxin Hu, Yi Lu, Xiangjia Zhu

{"title":"Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis.","authors":"Hao Li, Yu Du, Kaiwen Cheng, Yuxi Chen, Ling Wei, Yujun Pei, Xiaoyu Wang, Lan Wang, Ye Zhang, Xiaoxin Hu, Yi Lu, Xiangjia Zhu","doi":"10.1038/s41421-024-00709-5","DOIUrl":"10.1038/s41421-024-00709-5","url":null,"abstract":"High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM's gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072138","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

Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC. 突触后lncRNA Sera/Pkm2通路通过重塑mPFC的神经组合，协调从社会竞争到等级的转变。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-20 DOI: 10.1038/s41421-024-00706-8

Ling-Shuang Zhu, Chuan Lai, Chao-Wen Zhou, Hui-Yang Chen, Zhi-Qiang Liu, Ziyuan Guo, Hengye Man, Hui-Yun Du, Youming Lu, Feng Hu, Zhiye Chen, Kai Shu, Ling-Qiang Zhu, Dan Liu

{"title":"Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC.","authors":"Ling-Shuang Zhu, Chuan Lai, Chao-Wen Zhou, Hui-Yang Chen, Zhi-Qiang Liu, Ziyuan Guo, Hengye Man, Hui-Yun Du, Youming Lu, Feng Hu, Zhiye Chen, Kai Shu, Ling-Qiang Zhu, Dan Liu","doi":"10.1038/s41421-024-00706-8","DOIUrl":"10.1038/s41421-024-00706-8","url":null,"abstract":"Individuals' continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003714","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

Structural insight into 6-OH-FAD-dependent activation of hFSP1 for ferroptosis suppression. 从结构上洞察 6-OH-FAD 依赖性激活 hFSP1 以抑制铁变态反应。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-20 DOI: 10.1038/s41421-024-00723-7

Hongying Lan, Yu Gao, Ting Hong, Zihan Chang, Zhengyang Zhao, Yanfeng Wang, Feng Wang

引用次数: 0

Prediction of overall survival in stage II and III colon cancer through machine learning of rapidly-acquired proteomics. 通过对快速获得的蛋白质组学进行机器学习，预测 II 期和 III 期结肠癌患者的总生存期。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-13 DOI: 10.1038/s41421-024-00707-7

Kailun Xu, Xiaoyang Yin, Hui Chen, Yuhui Huang, Xi Zheng, Biting Zhou, Xue Cai, Huanhuan Gao, Miaomiao Tian, Sijun Hu, Shu Zheng, Changzheng Yuan, Yongzhan Nie, Tiannan Guo, Yingkuan Shao

引用次数: 0

Targeting cardiac fibrosis with chimeric antigen receptor macrophages. 用嵌合抗原受体巨噬细胞靶向心脏纤维化。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-13 DOI: 10.1038/s41421-024-00718-4

Zibei Gao, Lei Yan, Jufeng Meng, Zhengkai Lu, Kaixin Ge, Zhen Jiang, Teng Feng, Haopeng Wang, Chen Liu, Juan Tang, Hui Zhang

引用次数: 0

Structural basis for the interaction between human coronavirus HKU1 spike receptor binding domain and its receptor TMPRSS2. 人类冠状病毒 HKU1 穗状受体结合域与其受体 TMPRSS2 之间相互作用的结构基础。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-08 DOI: 10.1038/s41421-024-00717-5

Xiaopan Gao, Kaixiang Zhu, Lin Wang, Kun Shang, Lei Hua, Bo Qin, Hongtao Zhu, Wei Ding, Sheng Cui

引用次数: 0

40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice. 40赫兹的灯光闪烁可通过腺苷信号促进小鼠的甘液流。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-08-06 DOI: 10.1038/s41421-024-00701-z

Xiaoting Sun, Liliana Dias, Chenlei Peng, Ziyi Zhang, Haoting Ge, Zejun Wang, Jiayi Jin, Manli Jia, Tao Xu, Wei Guo, Wu Zheng, Yan He, Youru Wu, Xiaohong Cai, Paula Agostinho, Jia Qu, Rodrigo A Cunha, Xuzhao Zhou, Ruiliang Bai, Jiang-Fan Chen

{"title":"40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.","authors":"Xiaoting Sun, Liliana Dias, Chenlei Peng, Ziyi Zhang, Haoting Ge, Zejun Wang, Jiayi Jin, Manli Jia, Tao Xu, Wei Guo, Wu Zheng, Yan He, Youru Wu, Xiaohong Cai, Paula Agostinho, Jia Qu, Rodrigo A Cunha, Xuzhao Zhou, Ruiliang Bai, Jiang-Fan Chen","doi":"10.1038/s41421-024-00701-z","DOIUrl":"10.1038/s41421-024-00701-z","url":null,"abstract":"The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR-aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892984","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