The EMBO Journal最新文献_第3页

Heteroplasmy in action: tracking mtDNA segregation dynamics. 行动中的杂交：跟踪 mtDNA 的分离动态。

The EMBO Journal Pub Date : 2024-09-10 DOI: 10.1038/s44318-024-00226-x

Nitish Dua,Anjana Badrinarayanan

引用次数: 0

The global phosphorylation landscape of mouse oocytes during meiotic maturation. 小鼠卵母细胞减数分裂成熟过程中的全局磷酸化图谱

The EMBO Journal Pub Date : 2024-09-10 DOI: 10.1038/s44318-024-00222-1

Hongzheng Sun,Longsen Han,Yueshuai Guo,Huiqing An,Bing Wang,Xiangzheng Zhang,Jiashuo Li,Yingtong Jiang,Yue Wang,Guangyi Sun,Shuai Zhu,Shoubin Tang,Juan Ge,Minjian Chen,Xuejiang Guo,Qiang Wang

{"title":"The global phosphorylation landscape of mouse oocytes during meiotic maturation.","authors":"Hongzheng Sun,Longsen Han,Yueshuai Guo,Huiqing An,Bing Wang,Xiangzheng Zhang,Jiashuo Li,Yingtong Jiang,Yue Wang,Guangyi Sun,Shuai Zhu,Shoubin Tang,Juan Ge,Minjian Chen,Xuejiang Guo,Qiang Wang","doi":"10.1038/s44318-024-00222-1","DOIUrl":"https://doi.org/10.1038/s44318-024-00222-1","url":null,"abstract":"Phosphorylation is a key post-translational modification regulating protein function and biological outcomes. However, the phosphorylation dynamics orchestrating mammalian oocyte development remains poorly understood. In the present study, we apply high-resolution mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of mouse oocyte phosphorylation. Of more than 8000 phosphosites, 75% significantly oscillate and 64% exhibit marked upregulation during meiotic maturation, indicative of the dominant regulatory role. Moreover, we identify numerous novel phosphosites on oocyte proteins and a few highly conserved phosphosites in oocytes from different species. Through functional perturbations, we demonstrate that phosphorylation status of specific sites participates in modulating critical events including metabolism, translation, and RNA processing during meiosis. Finally, we combine inhibitor screening and enzyme-substrate network prediction to discover previously unexplored kinases and phosphatases that are essential for oocyte maturation. In sum, our data define landscape of the oocyte phosphoproteome, enabling in-depth mechanistic insights into developmental control of germ cells.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 the type I-F Cas8-HNH system. I-F 型 Cas8-HNH 系统的结构基础。

The EMBO Journal Pub Date : 2024-09-09 DOI: 10.1038/s44318-024-00229-8

Xuzichao Li,Yanan Liu,Jie Han,Lingling Zhang,Zhikun Liu,Lin Wang,Shuqin Zhang,Qian Zhang,Pengyu Fu,Hang Yin,Hongtao Zhu,Heng Zhang

{"title":"Structural basis for the type I-F Cas8-HNH system.","authors":"Xuzichao Li,Yanan Liu,Jie Han,Lingling Zhang,Zhikun Liu,Lin Wang,Shuqin Zhang,Qian Zhang,Pengyu Fu,Hang Yin,Hongtao Zhu,Heng Zhang","doi":"10.1038/s44318-024-00229-8","DOIUrl":"https://doi.org/10.1038/s44318-024-00229-8","url":null,"abstract":"The Cas3 nuclease is utilized by canonical type I CRISPR-Cas systems for processive target DNA degradation, while a newly identified type I-F CRISPR variant employs an HNH nuclease domain from the natural fusion Cas8-HNH protein for precise target cleavage both in vitro and in human cells. Here, we report multiple cryo-electron microscopy structures of the type I-F Cas8-HNH system at different functional states. The Cas8-HNH Cascade complex adopts an overall G-shaped architecture, with the HNH domain occupying the C-terminal helical bundle domain (HB) of the Cas8 protein in canonical type I systems. The Linker region connecting Cas8-NTD and HNH domains adopts a rigid conformation and interacts with the Cas7.6 subunit, enabling the HNH domain to be in a functional position. The full R-loop formation displaces the HNH domain away from the Cas6 subunit, thus activating the target DNA cleavage. Importantly, our results demonstrate that precise target cleavage is dictated by a C-terminal helix of the HNH domain. Together, our work not only delineates the structural basis for target recognition and activation of the type I-F Cas8-HNH system, but also guides further developments leveraging this system for precise DNA editing.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate 环四腺苷酸异位激活 CRISPR 核糖核酸酶 Csm6 的分子机制

The EMBO Journal Pub Date : 2023-12-19 DOI: 10.1038/s44318-023-00017-w

Liyang Du, Qinwei Zhu, Zhonghui Lin

引用次数: 0

The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover ER膜蛋白复合体通过控制BNIP3的周转限制有丝分裂

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00006-z

Jose M Delgado, Logan Wallace Shepard, Sarah W Lamson, Samantha L Liu, Christopher J Shoemaker

引用次数: 0

Dynamic coupling of fast channel gating with slow ATP-turnover underpins protein transport through the Sec translocon 快速通道门控与慢速 ATP 翻转的动态耦合是蛋白质通过 Sec 易位子转运的基础

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00004-1

Joel A. Crossley, W. Allen, Daniel W. Watkins, T. Sabir, S. Radford, Roman Tuma, I. Collinson, Tomas Fessl

引用次数: 0

YTHDC1 delays cellular senescence and pulmonary fibrosis by activating ATR in an m6A-independent manner YTHDC1 通过与 m6A 无关的方式激活 ATR 来延缓细胞衰老和肺纤维化

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00003-2

Canfeng Zhang, Liping Chen, Chen Xie, Fengwei Wang, Juan Wang, Haoxian Zhou, Qianyi Liu, Zhuo Zeng, Na Li, Junjiu Huang, Yong Zhao, Haiying Liu

引用次数: 0

Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400 从结构上深入了解 XIP 和 SEA0400 对人类钠-钙交换子 NCX1 的异位抑制作用

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00013-0

Yanli Dong, Zhuoya Yu, Yue Li, Bo Huang, Qinru Bai, Yiwei Gao, Qihao Chen, Na Li, Lingli He, Yan Zhao

引用次数: 0

The shelterin component TRF2 mediates columnar stacking of human telomeric chromatin 保护蛋白成分TRF2介导人类端粒染色质的柱状堆积

The EMBO Journal Pub Date : 2023-12-14 DOI: 10.1038/s44318-023-00002-3

S. Wong, Aghil Soman, N. Korolev, Wahyu Surya, Qinming Chen, Wayne Shum, John van Noort, L. Nordenskiöld

引用次数: 0

Extracellular vesicles and co-isolated endogenous retroviruses from murine cancer cells differentially affect dendritic cells 小鼠癌细胞中的细胞外囊泡和共同分离的内源性逆转录病毒对树突状细胞有不同影响

The EMBO Journal Pub Date : 2023-12-11 DOI: 10.15252/embj.2023113590

Federico Cocozza, Lorena Martin-Jaular, Lien Lippens, Aurelie Di Cicco, Yago A Arribas, Nicolas Ansart, Florent Dingli, Michael Richard, Louise Merle, Mabel Jouve San Roman, Patrick Poullet, Damarys Loew, Daniel Lévy, An Hendrix, George Kassiotis, Alain Joliot, Mercedes Tkach, Clotilde Théry

{"title":"Extracellular vesicles and co-isolated endogenous retroviruses from murine cancer cells differentially affect dendritic cells","authors":"Federico Cocozza, Lorena Martin-Jaular, Lien Lippens, Aurelie Di Cicco, Yago A Arribas, Nicolas Ansart, Florent Dingli, Michael Richard, Louise Merle, Mabel Jouve San Roman, Patrick Poullet, Damarys Loew, Daniel Lévy, An Hendrix, George Kassiotis, Alain Joliot, Mercedes Tkach, Clotilde Théry","doi":"10.15252/embj.2023113590","DOIUrl":"https://doi.org/10.15252/embj.2023113590","url":null,"abstract":"Cells secrete extracellular vesicles (EVs) and non-vesicular extracellular (nano)particles (NVEPs or ENPs) that may play a role in intercellular communication. Tumor-derived EVs have been proposed to induce immune priming of antigen presenting cells or to be immuno-suppressive agents. We suspect that such disparate functions are due to variable compositions in EV subtypes and ENPs. We aimed to characterize the array of secreted EVs and ENPs of murine tumor cell lines. Unexpectedly, we identified virus-like particles (VLPs) from endogenous murine leukemia virus in preparations of EVs produced by many tumor cells. We established a protocol to separate small EVs from VLPs and ENPs. We compared their protein composition and analyzed their functional interaction with target dendritic cells. ENPs were poorly captured and did not affect dendritic cells. Small EVs specifically induced dendritic cell death. A mixed large/dense EV/VLP preparation was most efficient to induce dendritic cell maturation and antigen presentation. Our results call for systematic re-evaluation of the respective proportions and functions of non-viral EVs and VLPs produced by murine tumors and their contribution to tumor progression.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0