Cell Research最新文献

{"title":"Stroke-induced trained immunity spells bad news for the heart","authors":"George Hajishengallis, Triantafyllos Chavakis","doi":"10.1038/s41422-024-01018-y","DOIUrl":"https://doi.org/10.1038/s41422-024-01018-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"95 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007530","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}

{"title":"Accurate de novo design of heterochiral protein-protein interactions.","authors":"Ke Sun, Sicong Li, Bowen Zheng, Yanlei Zhu, Tongyue Wang, Mingfu Liang, Yue Yao, Kairan Zhang, Jizhong Zhang, Hongyong Li, Dongyang Han, Jishen Zheng, Brian Coventry, Longxing Cao, David Baker, Lei Liu, Peilong Lu","doi":"10.1038/s41422-024-01014-2","DOIUrl":"https://doi.org/10.1038/s41422-024-01014-2","url":null,"abstract":"<p><p>Abiotic D-proteins that selectively bind to natural L-proteins have gained significant biotechnological interest. However, the underlying structural principles governing such heterochiral protein-protein interactions remain largely unknown. In this study, we present the de novo design of D-proteins consisting of 50-65 residues, aiming to target specific surface regions of L-proteins or L-peptides. Our designer D-protein binders exhibit nanomolar affinity toward an artificial L-peptide, as well as two naturally occurring proteins of therapeutic significance: the D5 domain of human tropomyosin receptor kinase A (TrkA) and human interleukin-6 (IL-6). Notably, these D-protein binders demonstrate high enantiomeric specificity and target specificity. In cell-based experiments, designer D-protein binders effectively inhibited the downstream signaling of TrkA and IL-6 with high potency. Moreover, these binders exhibited remarkable thermal stability and resistance to protease degradation. Crystal structure of the designed heterochiral D-protein-L-peptide complex, obtained at a resolution of 2.0 Å, closely resembled the design model, indicating that the computational method employed is highly accurate. Furthermore, the crystal structure provides valuable information regarding the interactions between helical L-peptides and D-proteins, particularly elucidating a novel mode of heterochiral helix-helix interactions. Leveraging the design of D-proteins specifically targeting L-peptides or L-proteins opens up avenues for systematic exploration of the mirror-image protein universe, paving the way for a diverse range of applications.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981833","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}

{"title":"NLRC5 PANoptosome: Aquaman of the Dead Sea.","authors":"Poonam S Jadhav, Shreya Mahajan, Si Ming Man","doi":"10.1038/s41422-024-01011-5","DOIUrl":"https://doi.org/10.1038/s41422-024-01011-5","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901089","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}

{"title":"SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma","authors":"Bisi Miao,&nbsp;Ling Ge,&nbsp;Chenxi He,&nbsp;Xinghao Wang,&nbsp;Jibo Wu,&nbsp;Xiang Li,&nbsp;Kun Chen,&nbsp;Jinkai Wan,&nbsp;Shenghui Xing,&nbsp;Lingnan Ren,&nbsp;Zhennan Shi,&nbsp;Shengnan Liu,&nbsp;Yajun Hu,&nbsp;Jiajia Chen,&nbsp;Yanyan Yu,&nbsp;Lijian Feng,&nbsp;Natasha M. Flores,&nbsp;Zhihui Liang,&nbsp;Xinyi Xu,&nbsp;Ruoxin Wang,&nbsp;Jian Zhou,&nbsp;Jia Fan,&nbsp;Bin Xiang,&nbsp;En Li,&nbsp;Yuanhui Mao,&nbsp;Jingdong Cheng,&nbsp;Kehao Zhao,&nbsp;Pawel K. Mazur,&nbsp;Jiabin Cai,&nbsp;Fei Lan","doi":"10.1038/s41422-024-01013-3","DOIUrl":"10.1038/s41422-024-01013-3","url":null,"abstract":"While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center, was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robust in vitro activity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma (HCC) and negatively correlated with patient prognosis. Depleting SMYD5 renders HCC cells hypersensitive to mTOR inhibition in both 2D and 3D cultures. Additionally, the loss of SMYD5 markedly inhibits HCC development and growth in both genetically engineered mouse and patient-derived xenograft (PDX) models, with the inhibitory effect in the PDX model further enhanced by concurrent mTOR suppression. Our findings reveal a novel role of the SMYD5 and RPL40 K22me3 axis in translation elongation and highlight the therapeutic potential of targeting SMYD5 in HCC, particularly with concurrent mTOR inhibition. This work also conceptually broadens the understanding of lysine methylation, extending its significance from transcriptional regulation to translational control.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 9","pages":"648-660"},"PeriodicalIF":28.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01013-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892990","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}

{"title":"Structural basis for linker histone H5–nucleosome binding and chromatin fiber compaction","authors":"Wenyan Li,&nbsp;Jie Hu,&nbsp;Feng Song,&nbsp;Juan Yu,&nbsp;Xin Peng,&nbsp;Shuming Zhang,&nbsp;Lin Wang,&nbsp;Mingli Hu,&nbsp;Jia-Cheng Liu,&nbsp;Yu Wei,&nbsp;Xue Xiao,&nbsp;Yan Li,&nbsp;Dongyu Li,&nbsp;Hui Wang,&nbsp;Bing-Rui Zhou,&nbsp;Linchang Dai,&nbsp;Zongjun Mou,&nbsp;Min Zhou,&nbsp;Haonan Zhang,&nbsp;Zheng Zhou,&nbsp;Huidong Zhang,&nbsp;Yawen Bai,&nbsp;Jin-Qiu Zhou,&nbsp;Wei Li,&nbsp;Guohong Li,&nbsp;Ping Zhu","doi":"10.1038/s41422-024-01009-z","DOIUrl":"10.1038/s41422-024-01009-z","url":null,"abstract":"The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 10","pages":"707-724"},"PeriodicalIF":28.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01009-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892991","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}

{"title":"Synergizing sequence and structure representations to predict protein variants","authors":"Tong Chen,&nbsp;Pranam Chatterjee","doi":"10.1038/s41422-024-01010-6","DOIUrl":"10.1038/s41422-024-01010-6","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 9","pages":"597-598"},"PeriodicalIF":28.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01010-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862135","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}

{"title":"Deciphering the role of immune system in the obesity-cancer relationship.","authors":"Camille Blériot, Gerasimos Anagnostopoulos, Florent Ginhoux","doi":"10.1038/s41422-024-01008-0","DOIUrl":"https://doi.org/10.1038/s41422-024-01008-0","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854989","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}

{"title":"Author Correction: Structural and functional evidence that GPR30 is not a direct estrogen receptor","authors":"Heng Liu,&nbsp;Shimeng Guo,&nbsp;Antao Dai,&nbsp;Peiyu Xu,&nbsp;Xin Li,&nbsp;Sijie Huang,&nbsp;Xinheng He,&nbsp;Kai Wu,&nbsp;Xinyue Zhang,&nbsp;Dehua Yang,&nbsp;Xin Xie,&nbsp;H. Eric Xu","doi":"10.1038/s41422-024-00998-1","DOIUrl":"10.1038/s41422-024-00998-1","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 9","pages":"669-669"},"PeriodicalIF":28.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00998-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792079","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}

{"title":"Yin and Yang of innate immune cell death.","authors":"Yaqiu Wang, Thirumala-Devi Kanneganti","doi":"10.1038/s41422-024-01007-1","DOIUrl":"https://doi.org/10.1038/s41422-024-01007-1","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765635","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}

{"title":"Can dental problems be indicative of clonal hematopoiesis?","authors":"Soichi Sano, Kenneth Walsh","doi":"10.1038/s41422-024-01006-2","DOIUrl":"https://doi.org/10.1038/s41422-024-01006-2","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"58 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755092","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}