Acta biochimica et biophysica Sinica最新文献_第6页

Structural basis for the inhibition of coronaviral main proteases by PF-00835231. PF-00835231 抑制冠状病毒主要蛋白酶的结构基础

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-29 DOI: 10.3724/abbs.2024122

Xuelan Zhou, Xiaolu Lu, Cheng Lin, Xiaofang Zou, Wenwen Li, Xiangyi Zeng, Jie Wang, Pei Zeng, Weiwei Wang, Jin Zhang, Haihai Jiang, Jian Li

{"title":"Structural basis for the inhibition of coronaviral main proteases by PF-00835231.","authors":"Xuelan Zhou, Xiaolu Lu, Cheng Lin, Xiaofang Zou, Wenwen Li, Xiangyi Zeng, Jie Wang, Pei Zeng, Weiwei Wang, Jin Zhang, Haihai Jiang, Jian Li","doi":"10.3724/abbs.2024122","DOIUrl":"https://doi.org/10.3724/abbs.2024122","url":null,"abstract":"The main protease (M pro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 M pro. Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 M pro and seven M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral M pros. In addition, the crystal structures of SARS-CoV-2 M pro, SARS-CoV M pro, MERS-CoV M pro, and seven SARS-CoV-2 M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral M pros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into M pro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

O-glycosylation of SARS-CoV-2 spike protein by host O-glycosyltransferase strengthens its trimeric structure. 宿主O-糖基转移酶对SARS-CoV-2尖峰蛋白的O-糖基化加强了其三聚体结构。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-26 DOI: 10.3724/abbs.2024127

Zhijue Xu, Han Zhang, Jiaqi Tian, Xin Ku, Rumeng Wei, Jingli Hou, Can Zhang, Fang Yang, Xia Zou, Yang Li, Hiroyuki Kaji, Sheng-Ce Tao, Atsushi Kuno, Wei Yan, Lin-Tai Da, Yan Zhang

{"title":"O-glycosylation of SARS-CoV-2 spike protein by host O-glycosyltransferase strengthens its trimeric structure.","authors":"Zhijue Xu, Han Zhang, Jiaqi Tian, Xin Ku, Rumeng Wei, Jingli Hou, Can Zhang, Fang Yang, Xia Zou, Yang Li, Hiroyuki Kaji, Sheng-Ce Tao, Atsushi Kuno, Wei Yan, Lin-Tai Da, Yan Zhang","doi":"10.3724/abbs.2024127","DOIUrl":"10.3724/abbs.2024127","url":null,"abstract":"Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus's entry into host cells and membrane fusion of the virus. However, the functions and relationship between host ppGalNAc-Ts and O-glycosylation on the S protein remain unclear. Herein, we identify 15 O-glycosites and 10 distinct O-glycan structures on the S protein using an HCD-product-dependent triggered ETD mass spectrometric analysis. We observe that the isoenzyme T6 of ppGalNAc-Ts (ppGalNAc-T6) exhibits high O-glycosylation activity for the S protein, as demonstrated by an on-chip catalytic assay. Overexpression of ppGalNAc-T6 in HEK293 cells significantly enhances the O-glycosylation level of the S protein, not only by adding new O-glycosites but also by increasing O-glycan heterogeneity. Molecular dynamics simulations reveal that O-glycosylation on the protomer-interface regions, modified by ppGalNAc-T6, potentially stabilizes the trimeric S protein structure by establishing hydrogen bonds and non-polar interactions between adjacent protomers. Furthermore, mutation frequency analysis indicates that most O-glycosites of the S protein are conserved during the evolution of SARS-CoV-2 variants. Taken together, our finding demonstrate that host O-glycosyltransferases dynamically regulate the O-glycosylation of the S protein, which may influence the trimeric structural stability of the protein. This work provides structural insights into the functional role of specific host O-glycosyltransferases in regulating the O-glycosylation of viral envelope proteins.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification and validation of disease severity-related circular RNA in acute pancreatitis. 鉴定和验证急性胰腺炎中与疾病严重程度相关的环状 RNA。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-25 DOI: 10.3724/abbs.2024115

Jiarong Li, Zefang Sun, Caihong Ning, Chiayen Lin, Dingcheng Shen, Gengwen Huang, Shuai Zhu, Lu Chen

引用次数: 0

Hedy: a groundbreaking revelation of cartilage oxygen homeostasis. Hedy：软骨氧平衡的突破性发现。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-22 DOI: 10.3724/abbs.2024116

Haoliang Hu, Labapuchi Labapuchi, Kerui Huang, Yanling Long, Linxi Chen

引用次数: 0

RNA structure in alternative splicing regulation: from mechanism to therapy. 替代剪接调控中的 RNA 结构：从机制到治疗。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-22 DOI: 10.3724/abbs.2024119

Nengcheng Bao, Zhechao Wang, Jiayan Fu, Haiyang Dong, Yongfeng Jin

{"title":"RNA structure in alternative splicing regulation: from mechanism to therapy.","authors":"Nengcheng Bao, Zhechao Wang, Jiayan Fu, Haiyang Dong, Yongfeng Jin","doi":"10.3724/abbs.2024119","DOIUrl":"https://doi.org/10.3724/abbs.2024119","url":null,"abstract":"Alternative splicing is a highly intricate process that plays a crucial role in post-transcriptional regulation and significantly expands the functional proteome of a limited number of coding genes in eukaryotes. Its regulation is multifactorial, with RNA structure exerting a significant impact. Aberrant RNA conformations lead to dysregulation of splicing patterns, which directly affects the manifestation of disease symptoms. In this review, the molecular mechanisms of RNA secondary structure-mediated splicing regulation are summarized, with a focus on the complex interplay between aberrant RNA conformations and disease phenotypes resulted from splicing defects. This study also explores additional factors that reshape structural conformations, enriching our understanding of the mechanistic network underlying structure-mediated splicing regulation. In addition, an emphasis has been placed on the clinical role of targeting aberrant splicing corrections in human diseases. The principal mechanisms of action behind this phenomenon are described, followed by a discussion of prospective development strategies and pertinent challenges.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury. ZIPK 与 STAT5A 合作，在高血糖诱导的血管损伤中参与 p53 介导的 ROS 积累。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-19 DOI: 10.3724/abbs.2024120

Qichao Wu, Tingting Xie, Chang Fu, Chenyu Sun, Yan Ma, Zhengzhe Huang, Jiao Yang, Xiaoxiao Li, Wenqian Li, Changhong Miao

{"title":"ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury.","authors":"Qichao Wu, Tingting Xie, Chang Fu, Chenyu Sun, Yan Ma, Zhengzhe Huang, Jiao Yang, Xiaoxiao Li, Wenqian Li, Changhong Miao","doi":"10.3724/abbs.2024120","DOIUrl":"https://doi.org/10.3724/abbs.2024120","url":null,"abstract":"In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5 mM) and high (25 mM) glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer. 乳酸通过 H3K18 乳化作用激活巨噬细胞中 CCL18 的表达，从而促进卵巢癌的肿瘤发生。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-12 DOI: 10.3724/abbs.2024111

Jinrui Sun, Qinmei Feng, Yue He, Ming Wang, Yumei Wu

{"title":"Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer.","authors":"Jinrui Sun, Qinmei Feng, Yue He, Ming Wang, Yumei Wu","doi":"10.3724/abbs.2024111","DOIUrl":"10.3724/abbs.2024111","url":null,"abstract":"This study investigates the role of lactate in the genesis and progression of ovarian cancer (OV) and explores the underlying mechanisms. Serum lactate levels show a positive correlation with tumor grade and poor prognosis in patients with OV. Bioinformatics analysis identifies CCL18 as a lactate-related gene in OV. CCL18 is up-regulated in cancerous tissues and positively related to serum lactate levels in OV patients. THP-1 cells are exposed to phorbol-12-myristate-13-acetate for M0 macrophage induction. The results of RT-qPCR and ELISA for M1/M2 macrophage-related markers and inflammatory cytokines show that the exposure of lactate to macrophages induces M2 polarization. Based on the coculture of OV cells with macrophages, lactate-treated macrophages induces a significant increase in the proliferation and migration of OV cells. However, these effects can be reversed by silencing of Gpr132 in macrophages or treatment with anti-CCL18 antibody. Experiments using the xenograft model verify that the oncogenic role of lactate in tumor growth and metastasis relies on Gpr132 and CCL18. ChIP-qPCR and luciferase reporter assays reveal that lactate regulates CCL18 expression via H3K18 lactylation. In conclusion, lactate is a potential therapeutic target for OV. It is involved in tumorigenesis by activating CCL18 expression via H3K18 lactylation in macrophages.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Lung metastases formed by disseminated tumor cells exhibit different proliferation states. 由扩散的肿瘤细胞形成的肺转移瘤表现出不同的增殖状态。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-08 DOI: 10.3724/abbs.2024118

Jiajun Liu, Shihui Liu, Jianhui Tian, Jiaxuan Li, Minghua Li, Zujun Que

引用次数: 0

Role of Emerin in regulating fibroblast differentiation and migration at the substrate of stiffness coupled topology. Emerin在调节成纤维细胞分化和迁移过程中的作用--刚性耦合拓扑基质

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-08 DOI: 10.3724/abbs.2024094

Tiantian Yang, Li Wang, Haiyang Ma, Kailun Li, Yajing Wang, Wenjie Tang, Zichen Wang, Meiwen An, Xiang Gao, Ludan Xu, Yunyun Guo, Jiqiang Guo, Yong Liu, Hugen Wang, Yang Liu, Quanyou Zhang

{"title":"Role of Emerin in regulating fibroblast differentiation and migration at the substrate of stiffness coupled topology.","authors":"Tiantian Yang, Li Wang, Haiyang Ma, Kailun Li, Yajing Wang, Wenjie Tang, Zichen Wang, Meiwen An, Xiang Gao, Ludan Xu, Yunyun Guo, Jiqiang Guo, Yong Liu, Hugen Wang, Yang Liu, Quanyou Zhang","doi":"10.3724/abbs.2024094","DOIUrl":"10.3724/abbs.2024094","url":null,"abstract":"In hypertrophic scars, the differentiation and migration of fibroblasts are influenced by the extracellular matrix microenvironment, which includes factors such as stiffness, restraint, and tensile force. These mechanical stresses incite alterations in cell behavior, accompanied by cytoskeletal protein reorganization. However, the role of nucleo-skeletal proteins in this context remains underexplored. In this study, we use a polyacrylamide hydrogel (PAA) to simulate the mechanical stress experienced by cells in scar tissue and investigate the impact of Emerin on cell behavior. We utilize atomic force microscopy (AFM) and RNA interference technology to analyze cell differentiation, migration, and stiffness. Our findings reveal that rigid substrates and cellular restriction elevate Emerin expression and diminish differentiation. Conversely, reducing Emerin expression leads to attenuated cell differentiation, where stiffness and constraining factors exert no notable influence. Furthermore, a softening of cells and an enhanced migration rate are also markedly observed. These observations indicate that variations in nuclear skeletal proteins, prompted by diverse matrix microenvironments, play a pivotal role in the pathogenesis of hypertrophic scars (HSs). This research offers novel insights and a reference point for understanding scar fibrosis formation mechanisms and preventing fibrosis.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma. SEC61 Translocon gamma 亚基与糖酵解活性、上皮间质转化和肺腺癌的免疫抑制表型相关。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-07-08 DOI: 10.3724/abbs.2024109

Changshuai Zhou, Huanhuan Cui, Yuechao Yang, Lei Chen, Mingtao Feng, Yang Gao, Deheng Li, Liangdong Li, Xin Chen, Xiaoqiu Li, Yiqun Cao

{"title":"SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.","authors":"Changshuai Zhou, Huanhuan Cui, Yuechao Yang, Lei Chen, Mingtao Feng, Yang Gao, Deheng Li, Liangdong Li, Xin Chen, Xiaoqiu Li, Yiqun Cao","doi":"10.3724/abbs.2024109","DOIUrl":"https://doi.org/10.3724/abbs.2024109","url":null,"abstract":"Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant downregulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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