The FEBS journal最新文献_第10页

Decoy peptides that inhibit TNF signaling by disrupting the TNF homotrimeric oligomer 诱饵肽，通过破坏 TNF 同源三聚体寡聚体来抑制 TNF 信号传导。

The FEBS journal Pub Date : 2024-07-14 DOI: 10.1111/febs.17220

Nasir Javaid, Bilal Ahmad, Mahesh Chandra Patra, Sangdun Choi

{"title":"Decoy peptides that inhibit TNF signaling by disrupting the TNF homotrimeric oligomer","authors":"Nasir Javaid, Bilal Ahmad, Mahesh Chandra Patra, Sangdun Choi","doi":"10.1111/febs.17220","DOIUrl":"10.1111/febs.17220","url":null,"abstract":"Tumor necrosis factor (TNF) is a pro-inflammatory cytokine and its functional homotrimeric form interacts with the TNF receptor (TNFR) to activate downstream apoptotic, necroptotic, and inflammatory signaling pathways. Excessive activation of these pathways leads to various inflammatory diseases, which makes TNF a promising therapeutic target. Here, 12-mer peptides were selected from the interface of TNF-TNFR based upon their relative binding energies and were named ‘TNF-inhibiting decoys’ (TIDs). These decoy peptides inhibited TNF-mediated secretion of cytokines and cell death, as well as activation of downstream signaling effectors. Effective TIDs inhibited TNF signaling by disrupting the formation of TNF's functional homotrimeric form. Among derivatives of TIDs, TID3c showed slightly better efficacy in cell-based assays by disrupting TNF trimer formation. Moreover, TID3c oligomerized TNF to a high molecular weight configuration. In silico modeling and simulations revealed that TID3c and its parent peptide, TID3, form a stable complex with TNF through hydrogen bonds and electrostatic interactions, which makes them the promising lead to develop peptide-based anti-TNF therapeutics.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604720","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

6-Phosphogluconolactonase is critical for the efficient functioning of the pentose phosphate pathway 6- 磷酸葡萄糖酸内酯酶对磷酸戊糖途径的高效运作至关重要。

The FEBS journal Pub Date : 2024-07-10 DOI: 10.1111/febs.17221

Léa Phégnon, Julien Pérochon, Sandrine Uttenweiler-Joseph, Edern Cahoreau, Pierre Millard, Fabien Létisse

{"title":"6-Phosphogluconolactonase is critical for the efficient functioning of the pentose phosphate pathway","authors":"Léa Phégnon, Julien Pérochon, Sandrine Uttenweiler-Joseph, Edern Cahoreau, Pierre Millard, Fabien Létisse","doi":"10.1111/febs.17221","DOIUrl":"10.1111/febs.17221","url":null,"abstract":"The metabolic networks of microorganisms are remarkably robust to genetic and environmental perturbations. This robustness stems from redundancies such as gene duplications, isoenzymes, alternative metabolic pathways, and also from non-enzymatic reactions. In the oxidative branch of the pentose phosphate pathway (oxPPP), 6-phosphogluconolactone hydrolysis into 6-phosphogluconate is catalysed by 6-phosphogluconolactonase (Pgl) but in the absence of the latter, the oxPPP flux is thought to be maintained by spontaneous hydrolysis. However, in Δpgl Escherichia coli, an extracellular pathway can also contribute to pentose phosphate synthesis. This raises question as to whether the intracellular non-enzymatic reaction can compensate for the absence of 6-phosphogluconolactonase and, ultimately, on the role of 6-phosphogluconolactonase in central metabolism. Our results validate that the bypass pathway is active in the absence of Pgl, specifically involving the extracellular spontaneous hydrolysis of gluconolactones to gluconate. Under these conditions, metabolic flux analysis reveals that this bypass pathway accounts for the entire flux into the oxPPP. This alternative metabolic route—partially extracellular—sustains the flux through the oxPPP necessary for cell growth, albeit at a reduced rate in the absence of Pgl. Importantly, these findings imply that intracellular non-enzymatic hydrolysis of 6-phosphogluconolactone does not compensate for the absence of Pgl. This underscores the crucial role of Pgl in ensuring the efficient functioning of the oxPPP.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.17221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MediatorWeb: a protein–protein interaction network database for the RNA polymerase II Mediator complex MediatorWeb：RNA 聚合酶 II Mediator 复合物的蛋白质-蛋白质相互作用网络数据库。

The FEBS journal Pub Date : 2024-07-08 DOI: 10.1111/febs.17225

Sourobh Maji, Mohd Waseem, Manish Kumar Sharma, Maninder Singh, Anamika Singh, Nidhi Dwivedi, Pallabi Thakur, David G. Cooper, Naveen C. Bisht, Jan S. Fassler, Naidu Subbarao, Jitendra P. Khurana, Neel Sarovar Bhavesh, Jitendra Kumar Thakur

{"title":"MediatorWeb: a protein–protein interaction network database for the RNA polymerase II Mediator complex","authors":"Sourobh Maji, Mohd Waseem, Manish Kumar Sharma, Maninder Singh, Anamika Singh, Nidhi Dwivedi, Pallabi Thakur, David G. Cooper, Naveen C. Bisht, Jan S. Fassler, Naidu Subbarao, Jitendra P. Khurana, Neel Sarovar Bhavesh, Jitendra Kumar Thakur","doi":"10.1111/febs.17225","DOIUrl":"10.1111/febs.17225","url":null,"abstract":"The protein–protein interaction (PPI) network of the Mediator complex is very tightly regulated and depends on different developmental and environmental cues. Here, we present an interactive platform for comparative analysis of the Mediator subunits from humans, baker's yeast Saccharomyces cerevisiae, and model plant Arabidopsis thaliana in a user-friendly web-interface database called MediatorWeb. MediatorWeb provides an interface to visualize and analyze the PPI network of Mediator subunits. The database facilitates downloading the untargeted and unweighted network of Mediator complex, its submodules, and individual Mediator subunits to better visualize the importance of individual Mediator subunits or their submodules. Further, MediatorWeb offers network visualization of the Mediator complex and interacting proteins that are functionally annotated. This feature provides clues to understand functions of Mediator subunits in different processes. In an additional tab, MediatorWeb provides quick access to secondary and tertiary structures, as well as residue–level contact information for Mediator subunits in each of the three model organisms. Another useful feature of MediatorWeb is detection of interologs based on orthologous analyses, which can provide clues to understand the functions of Mediator complex in less explored kingdoms. Thus, MediatorWeb and its features can help the user to understand the role of Mediator complex and its subunits in the transcription regulation of gene expression.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556243","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

TRAF2 associates with cullin neddylation complex assembly TRAF2与cullin奈德化复合体的组装有关。

The FEBS journal Pub Date : 2024-07-08 DOI: 10.1111/febs.17222

Tiantian Wang, Qi Zhang, Yu Xu, Rong Yan, Yuting Pan, Ying Xuan, Mengzhen Shen, Xianzhi Chen, Hongyan Zhu, Xisong Ke, Yi Qu, Xue Zhang

{"title":"TRAF2 associates with cullin neddylation complex assembly","authors":"Tiantian Wang, Qi Zhang, Yu Xu, Rong Yan, Yuting Pan, Ying Xuan, Mengzhen Shen, Xianzhi Chen, Hongyan Zhu, Xisong Ke, Yi Qu, Xue Zhang","doi":"10.1111/febs.17222","DOIUrl":"10.1111/febs.17222","url":null,"abstract":"Cullin-based RING ligases (CRLs) comprise the largest family of ubiquitin E3 ligases. CRL activity is tightly regulated by cullin neddylation, which has been associated with various diseases. Although inhibitors of CRLs neddylation have been reported, there is a lack of small molecules that can selectively target individual cullins. Here, we identified a natural product, liquidambaric acid (LDA), with relatively selective inhibition properties against cullin (Cul) 2 neddylation, and found that its target, Tumor Necrosis Factor receptor-associated factor 2 (TRAF2) was required for the activity. TRAF2 associates with the Cul2 neddylation complex and regulates the machinery assembly, especially that of E2 (UBC12) and E3 (RBX1) enzymes. In addition, we demonstrated that by intervention of the associations between TRAF2 and the neddylation machinery, LDA disturbed NEDD8 transfer from E1 to E2, therefore blocking Cul2 neddylation. Taken together, we show that TRAF2 plays a positive role in neddylation cascades, and we have identified a small molecule capable of selective modulation of cullin neddylation.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560668","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

Type I Hsp40s/DnaJs aggregates exhibit features reminiscent of amyloidogenic structures I 型 Hsp40s/DnaJs 聚集体表现出与淀粉样蛋白生成结构相似的特征。

The FEBS journal Pub Date : 2024-07-08 DOI: 10.1111/febs.17215

Ana O. Tiroli-Cepeda, Leonardo A. Linhares, Annelize Z. B. Aragão, Jemmyson R. de Jesus, Ana P. Wasilewska-Sampaio, Fernanda G. De Felice, Sérgio T. Ferreira, Júlio C. Borges, Douglas M. Cyr, Carlos H. I. Ramos

{"title":"Type I Hsp40s/DnaJs aggregates exhibit features reminiscent of amyloidogenic structures","authors":"Ana O. Tiroli-Cepeda, Leonardo A. Linhares, Annelize Z. B. Aragão, Jemmyson R. de Jesus, Ana P. Wasilewska-Sampaio, Fernanda G. De Felice, Sérgio T. Ferreira, Júlio C. Borges, Douglas M. Cyr, Carlos H. I. Ramos","doi":"10.1111/febs.17215","DOIUrl":"10.1111/febs.17215","url":null,"abstract":"A rise in temperature triggers a structural change in the human Type I 40 kDa heat shock protein (Hsp40/DnaJ), known as DNAJA1. This change leads to a less compact structure, characterized by an increased presence of solvent-exposed hydrophobic patches and β-sheet-rich regions. This transformation is validated by circular dichroism, thioflavin T binding, and Bis-ANS assays. The formation of this β-sheet-rich conformation, which is amplified in the absence of zinc, leads to protein aggregation. This aggregation is induced not only by high temperatures but also by low ionic strength and high protein concentration. The aggregated conformation exhibits characteristics of an amyloidogenic structure, including a distinctive X-ray diffraction pattern, seeding competence (which stimulates the formation of amyloid-like aggregates), cytotoxicity, resistance to SDS, and fibril formation. Interestingly, the yeast Type I Ydj1 also tends to adopt a similar β-sheet-rich structure under comparable conditions, whereas Type II Hsp40s, whether human or from yeast, do not. Moreover, Ydj1 aggregates were found to be cytotoxic. Studies using DNAJA1- and Ydj1-deleted mutants suggest that the zinc-finger region plays a crucial role in amyloid formation. Our discovery of amyloid aggregation in a C-terminal deletion mutant of DNAJA1, which resembles a spliced homolog expressed in the testis, implies that Type I Hsp40 co-chaperones may generate amyloidogenic species in vivo.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556245","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

The role of interleukin-6 family cytokines in cancer cachexia 白细胞介素-6 家族细胞因子在癌症恶病质中的作用

The FEBS journal Pub Date : 2024-07-08 DOI: 10.1111/febs.17224

Samet Agca, Serkan Kir

引用次数: 0

Histamine promotes mouse decidualization through stimulating epithelial amphiregulin release 组胺通过刺激上皮细胞两性胰岛素的释放来促进小鼠蜕皮。

The FEBS journal Pub Date : 2024-07-07 DOI: 10.1111/febs.17219

Cheng-Kan Liu, Yu-Ying He, Si-Ting Chen, Wen-Wen Shi, Ying Wang, Hui-Na Luo, Zeng-Ming Yang

{"title":"Histamine promotes mouse decidualization through stimulating epithelial amphiregulin release","authors":"Cheng-Kan Liu, Yu-Ying He, Si-Ting Chen, Wen-Wen Shi, Ying Wang, Hui-Na Luo, Zeng-Ming Yang","doi":"10.1111/febs.17219","DOIUrl":"10.1111/febs.17219","url":null,"abstract":"Accumulating evidence shows that inflammation is essential for embryo implantation and decidualization. Histamine, a proinflammatory factor that is present in almost all mammalian tissues, is synthesized through decarboxylating histidine by histidine decarboxylase (HDC). Although histamine is known to be essential for decidualization, the underlying mechanism remains undefined. In the present study, histamine had no obvious direct effects on in vitro decidualization in mice. However, the obvious differences in HDC protein levels between day 4 of pregnancy and day 4 of pseudopregnancy, as well as between delayed and activated implantation, suggested that the blastocyst may be involved in regulating HDC expression. Furthermore, blastocyst-derived tumor necrosis factor α (TNFα) significantly increased HDC levels in the luminal epithelium. Histamine increased the levels of amphiregulin (AREG) and disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) proteins, which was abrogated by treatment with famotidine, a specific histamine type 2 receptor (H2R) inhibitor, or by TPAI-1 (a specific inhibitor of ADAM17). Intraluminal injection of urocanic acid (HDC inhibitor) on day 4 of pregnancy significantly reduced the number of implantation sites on day 5 of pregnancy. TNFα-stimulated increases in HDC, AREG and ADAM17 protein levels was abrogated by urocanic acid, a specific inhibitor of HDC. Additionally, AREG treatment significantly promoted in vitro decidualization. Collectively, our data suggests that blastocyst-derived TNFα induces luminal epithelial histamine secretion, and histamine increases mouse decidualization through ADAM17-mediated AREG release.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556241","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

Biochemical, kinetic, and structural characterization of a Bacillus tequilensis nitroreductase 茶碱芽孢杆菌硝基还原酶的生物化学、动力学和结构特征。

The FEBS journal Pub Date : 2024-07-01 DOI: 10.1111/febs.17210

Sara Russo, Henriette J. Rozeboom, Hein J. Wijma, Gerrit J. Poelarends, Marco W. Fraaije

{"title":"Biochemical, kinetic, and structural characterization of a Bacillus tequilensis nitroreductase","authors":"Sara Russo, Henriette J. Rozeboom, Hein J. Wijma, Gerrit J. Poelarends, Marco W. Fraaije","doi":"10.1111/febs.17210","DOIUrl":"10.1111/febs.17210","url":null,"abstract":"Nitroreductases (NRs) are NAD(P)H-dependent flavoenzymes that reduce nitro aromatic compounds to their corresponding arylamines via the nitroso and hydroxylamine intermediates. Because of their broad substrate scope and versatility, NRs have found application in multiple fields such as biocatalysis, bioremediation, cell-imaging and prodrug activation. However, only a limited number of members of the broad NR superfamily (> 24 000 sequences) have been experimentally characterized. Within this group of enzymes, only few are capable of amine synthesis, which is a fundamental chemical transformation for the pharmaceutical, agricultural, and textile industries. Herein, we provide a comprehensive description of a recently discovered NR from Bacillus tequilensis, named BtNR. This enzyme has previously been demonstrated to have the capability to fully convert nitro aromatic and heterocyclic compounds to their respective primary amines. In this study, we determined its biochemical, kinetic and structural properties, including its apparent melting temperature (Tm) of 59 °C, broad pH activity range (from pH 3 to 10) and a notably low redox potential (−236 ± 1 mV) in comparison to other well-known NRs. We also determined its steady-state and pre-steady-state kinetic parameters, which are consistent with other NRs. Additionally, we elucidated the crystal structure of BtNR, which resembles the well-characterized Escherichia coli oxygen-insensitive NAD(P)H nitroreductase (NfsB), and investigated the substrate binding in its active site through docking and molecular dynamics studies with four nitro aromatic substrates. Guided by these structural analyses, we probed the functional roles of active site residues by site-directed mutagenesis. Our findings provide valuable insights into the biochemical and structural properties of BtNR, as well as its potential applications in biotechnology.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.17210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIM2 promotes metabolic adaptation to glutamine deprivation via enhancement of CPT1A activity. TRIM2 通过增强 CPT1A 的活性促进对谷氨酰胺缺乏的代谢适应。

The FEBS journal Pub Date : 2024-07-01 DOI: 10.1111/febs.17218

Kaimin Liao, Kaiyue Liu, Zhongyu Wang, Kailiang Zhao, Yide Mei

引用次数: 0

Dysregulated ribosome quality control in human diseases. 人类疾病中的核糖体质量控制失调。

The FEBS journal Pub Date : 2024-07-01 DOI: 10.1111/febs.17217

Tom McGirr, Okan Onar, Seyed Mehdi Jafarnejad

引用次数: 0