FEBS Letters最新文献_第2页

Binding mechanism of adenylate kinase-specific monobodies. 腺苷酸激酶特异性单体的结合机制。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-21 DOI: 10.1002/1873-3468.70076

Ibuki Nakamura, Hiroshi Amesaka, Satoshi Nagao, Naoki Orito, Shigeru Negi, Shun-Ichi Tanaka, Takashi Matsuo

引用次数: 0

B cell mechanobiology in health and disease: emerging techniques and insights into therapeutic responses. 健康和疾病中的B细胞机械生物学：新兴技术和对治疗反应的见解。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-19 DOI: 10.1002/1873-3468.70071

Marta Sampietro, Marco Cellani, Cristina Scielzo

{"title":"B cell mechanobiology in health and disease: emerging techniques and insights into therapeutic responses.","authors":"Marta Sampietro, Marco Cellani, Cristina Scielzo","doi":"10.1002/1873-3468.70071","DOIUrl":"https://doi.org/10.1002/1873-3468.70071","url":null,"abstract":"Cells sense physical cues from their environment and convert them into biochemical responses through mechanotransduction. Unlike solid tumours, the role of such forces in haematological cancers is underexplored. In this context, immune cells experience dynamic mechanical stimuli as they migrate, extravasate and home to specific tissues. Understanding how these forces shape B-cell function and malignancy represents a groundbreaking area of research. This review examines the key mechanosensory pathways and molecules involved in lymphocyte mechanotransduction, beginning with mechanosensory proteins at the plasma membrane, followed by intracellular signal propagation through the cytoskeleton, eventually highlighting the nucleus as a 'signal actuator'. Subsequently, we cover some measurement approaches and advanced systems to investigate tumour biomechanics, highlighting their application in the context of B cells. Finally, we focus on the implications of mechanobiology in leukaemia, identifying molecules involved in B-cell malignancies that could serve as potential 'mechano-targets' for personalised therapies. This review emphasises the need to understand how lymphocytes generate, sense and respond to mechanical stimuli, which could open avenues for future biomedical innovations. Impact statement Our review is particularly valuable in highlighting the underexplored role of mechanobiology in B cell function and malignancies, while also discussing emerging techniques that can advance this research area. It bridges mechanotransduction, immunology, and cancer biology in a way that will be of interest to researchers across these three main fields.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Biophysical characterization of a putative antimicrobial peptide-binding protein of Escherichia coli highlights its dual functionality. 一种推定的抗菌肽结合蛋白的生物物理特性突出了其双重功能。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-19 DOI: 10.1002/1873-3468.70068

Pratik Dasgupta, Shankar Prasad Kanaujia

{"title":"Biophysical characterization of a putative antimicrobial peptide-binding protein of Escherichia coli highlights its dual functionality.","authors":"Pratik Dasgupta, Shankar Prasad Kanaujia","doi":"10.1002/1873-3468.70068","DOIUrl":"https://doi.org/10.1002/1873-3468.70068","url":null,"abstract":"Antimicrobial peptides (AMPs) disrupt the integrity of the bacterial membrane, ultimately leading to their death. In counter-defense, pathogens are reported to have developed systems such as the sensitivity to antimicrobial peptides (Sap) transport system that evade the action of AMPs and sequester essential micronutrients. However, recent contrasting reports cloud the functional prospects of the Sap system. Hence, this study aimed to characterize the Escherichia coli Sap (EcSap) transport system using biophysical techniques. The results obtained from various approaches suggested the binding of heme to the substrate-binding component (EcSapA) of the EcSap system. Further, this study suggests the interaction of EcSapA with the AMP protamine. In summary, the findings of this study suggest the dual ligand-binding ability of EcSapA. Impact statement The present study reports the functional prospects of the enigmatic substrate-binding protein SapA of E. coli. This analysis highlights the essentiality of the intra-protein disulfide bonds in maintaining the structural integrity of EcSapA. Further, biophysical studies of EcSapA highlight its dual ligand binding propensity, earmarking it as a drug target.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Molecular insights into RNA recognition by the ZAR1 C-terminal domain. ZAR1 c端结构域对RNA识别的分子见解。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-19 DOI: 10.1002/1873-3468.70080

Qingling Liu, Haoyu Ma, Xian He, Chao Xu, Jiahai Zhang

引用次数: 0

In vivo evidence for glycyl radical insertion into a catalytically inactive variant of pyruvate formate-lyase. 体内证据表明，甘酰基自由基插入到催化无活性的丙酮酸甲酸裂解酶变体。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-19 DOI: 10.1002/1873-3468.70075

Michelle Kammel, A F Volker Wagner, R Gary Sawers

{"title":"In vivo evidence for glycyl radical insertion into a catalytically inactive variant of pyruvate formate-lyase.","authors":"Michelle Kammel, A F Volker Wagner, R Gary Sawers","doi":"10.1002/1873-3468.70075","DOIUrl":"https://doi.org/10.1002/1873-3468.70075","url":null,"abstract":"The dimeric glycyl radical enzyme pyruvate formate-lyase (PflB; formate acetyltransferase 1) cleaves pyruvate with hypothetical half-site reactivity to formate and acetyl-CoA. The radical introduced onto residue G734 of PflB is transiently transferred to C419 of an adjacent cysteine pair (C418/C419) during catalysis, but it is unclear whether glycyl radical formation is dependent on C419 in vivo. We show here that a deficiency in formate production of an Escherichia coli strain synthesizing a PflBG734A variant, but lacking the autonomous glycyl radical cofactor, GrcA, could be restored by reintroducing plasmid-encoded native PflB, but not by a PflBC418A/C419A variant, indicating that PflBC418A/C419A cannot replace GrcA. Oxygen-dependent polypeptide cleavage of PflBC418A/C419A indicated stable glycyl radical incorporation; however, these data did not support half-site reactivity. These in vivo findings demonstrate that glycyl radical formation is independent of subsequent radical transfer from G734 to C419, which occurs intramolecularly. Impact statement Active, dimeric pyruvate formate-lyase has a stable radical on a glycine residue, which transiently abstracts a H-atom from a cysteine, generating a catalytic thiyl radical. Glycyl radical generation is independent of glycine-to-cysteine radical-transfer in vivo. Radical-transfer is intramolecular and the enzyme does not appear to exhibit half-site reactivity.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

E3 ubiquitin ligase RMND5A maintains the self-renewal state of human neural stem/precursor cells by regulating Wnt and mTOR signaling pathways. E3泛素连接酶RMND5A通过调节Wnt和mTOR信号通路维持人神经干/前体细胞的自我更新状态。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-16 DOI: 10.1002/1873-3468.70067

Takumi Nakagawa, Kosuke Hata, Yoshihiro Izumi, Hideyuki Nakashima, Sayako Katada, Taito Matsuda, Takeshi Bamba, Kinichi Nakashima

{"title":"E3 ubiquitin ligase RMND5A maintains the self-renewal state of human neural stem/precursor cells by regulating Wnt and mTOR signaling pathways.","authors":"Takumi Nakagawa, Kosuke Hata, Yoshihiro Izumi, Hideyuki Nakashima, Sayako Katada, Taito Matsuda, Takeshi Bamba, Kinichi Nakashima","doi":"10.1002/1873-3468.70067","DOIUrl":"https://doi.org/10.1002/1873-3468.70067","url":null,"abstract":"During cortical development, neural stem/precursor cells (NS/PCs) sequentially produce neurons, astrocytes, and oligodendrocytes. Before producing these cells, human (h) NS/PCs undergo prolonged self-renewal to form a larger cortex than other mammals, although the mechanisms are mostly unknown. Here, we performed a gene knockout screen using the CRISPR/Cas9 system to search for genes involved in hNS/PC self-renewal. We identified RMND5A, encoding an E3 ubiquitin ligase, among the candidate genes. We further demonstrated that knockdown of RMND5A decreased proliferation and promoted neuronal differentiation of hNS/PCs through the activation and suppression of the Wnt and mTOR signaling pathways, respectively. Taken together, our findings suggest that RMND5A participates in the maintenance of hNS/PC self-renewal by modulating the Wnt and mTOR signaling pathways. Impact statement During cortical development, human neural stem/precursor cells (hNS/PCs) undergo prolonged self-renewal to form a larger cortex than other mammals, although the mechanisms are mostly unknown. We identified RMND5A, an E3 ubiquitin ligase, as essential for maintaining self-renewal of hNS/PCs, providing valuable insights into the evolutionary expansion of the human brain.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The carboxylate "gripper" of the substrate is critical for C-4 stereo-inversion by UDP-glucuronic acid 4-epimerase. 底物的羧酸“夹持器”对于udp -葡萄糖醛酸-4 -甲酰基酶的C-4立体转化至关重要。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-16 DOI: 10.1002/1873-3468.70070

Annika J E Borg, Laura De Cnop, Bernd Nidetzky

引用次数: 0

Structural and functional consequences of the cardiomyopathy-associated p.R157C mutation in the C-terminal palindromic motif of human αB-crystallin. 人α b -结晶蛋白c端回文基序中与心肌病相关的p.R157C突变的结构和功能后果

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70043

Leila Rezaei Somee, Parisa Ebrahimi, Giulio Agnetti, Mansi Upadhyay, Rahul Shobhawat, Ashutosh Kumar, Mohammad Bagher Shahsavani, Issa Zarei, Massoud Amanlou, Ali Akbar Saboury, Ali Akbar Moosavi-Movahedi, Reza Yousefi

{"title":"Structural and functional consequences of the cardiomyopathy-associated p.R157C mutation in the C-terminal palindromic motif of human αB-crystallin.","authors":"Leila Rezaei Somee, Parisa Ebrahimi, Giulio Agnetti, Mansi Upadhyay, Rahul Shobhawat, Ashutosh Kumar, Mohammad Bagher Shahsavani, Issa Zarei, Massoud Amanlou, Ali Akbar Saboury, Ali Akbar Moosavi-Movahedi, Reza Yousefi","doi":"10.1002/1873-3468.70043","DOIUrl":"https://doi.org/10.1002/1873-3468.70043","url":null,"abstract":"αB-crystallin, a small heat shock protein, is crucial for maintaining lenticular transparency and prevents protein aggregation as a molecular chaperone in various tissues. Mutations in αB-crystallin can lead to diseases such as cataracts, cardiomyopathy, and neurodegenerative disorders. This study explores the effects of the p.R157C mutation in the C-terminal domain, near the IXI motif, which is associated with cardiomyopathy. The mutant protein was generated through site-directed mutagenesis, expressed in bacterial systems, and purified by ion-exchange chromatography. Biophysical and computational techniques revealed significant alterations in secondary structure, oligomerization, and conformational stability. The mutation also enhanced chaperone activity and promoted amyloid fibril formation. These alterations may disrupt the interactions of the p.R157C mutant αB-crystallin with cardiac proteins such as desmin and calcineurin, potentially contributing to cardiomyopathy. These findings offer mechanistic insights into αB-crystallin-related cardiomyopathy, shedding light on its pathological role and potential therapeutic targets.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The bacteriolytic activity of the putative holin Gp52 of bacteriophage Phi11 requires its N-terminal transmembrane domains. 噬菌体Phi11的假定持有蛋白Gp52的溶菌活性需要其n端跨膜结构域。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70062

Manideep Burra, Vijay Hemmadi, Vivek Ratre, Malabika Biswas

{"title":"The bacteriolytic activity of the putative holin Gp52 of bacteriophage Phi11 requires its N-terminal transmembrane domains.","authors":"Manideep Burra, Vijay Hemmadi, Vivek Ratre, Malabika Biswas","doi":"10.1002/1873-3468.70062","DOIUrl":"https://doi.org/10.1002/1873-3468.70062","url":null,"abstract":"Gene gp52 of bacteriophage Phi11 encodes a putative holin (\"GeneID:1258070\"). Holins are bacteriophage proteins that control host cell lysis and determine the timing of the phage's infectious cycle. This study assessed the effect of overexpressing Gp52 and its mutants upon the growth rate and morphology of Escherichia coli. Gp52 caused aggressive host cell lysis, while two of the deletion mutants caused a decline in lytic potency. Lysis was completely abolished by the third mutant, which lacked the N-terminal domain and the two putative transmembrane domains. This is a first-hand study reporting the domain-dependent antibacterial activity of Gp52 and could contribute to the development of novel therapeutic interventions targeting bacterial membrane integrity, especially in the context of rising antimicrobial resistance. Impact statement We studied the functional domains of Phi11 holin and their impact on host lysis. The identification of the smallest region of holin which can lyse bacterial cells will open doors for novel phage-based therapies, thereby circumventing traditional antibiotics and benefiting both the scientific community and society's fight against antimicrobial resistance.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Structure-based identification of herbacetin and caffeic acid phenethyl ester as inhibitors of S-adenosylmethionine-dependent viral methyltransferase. 基于结构的草菌素和咖啡酸苯乙酯作为s -腺苷甲硫氨酸依赖性病毒甲基转移酶抑制剂的鉴定。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-05-12 DOI: 10.1002/1873-3468.70054

Mandar Bhutkar, Amith Kumar, Ruchi Rani, Vishakha Singh, Ankita Saha, Akashjyoti Pathak, Aditi Kothiala, Supreeti Mahajan, Bhairavnath Waghmode, Shalja Verma, Ravi Kumar, Rajat Mudgal, Debabrata Sircar, Pravindra Kumar, Shailly Tomar

{"title":"Structure-based identification of herbacetin and caffeic acid phenethyl ester as inhibitors of S-adenosylmethionine-dependent viral methyltransferase.","authors":"Mandar Bhutkar, Amith Kumar, Ruchi Rani, Vishakha Singh, Ankita Saha, Akashjyoti Pathak, Aditi Kothiala, Supreeti Mahajan, Bhairavnath Waghmode, Shalja Verma, Ravi Kumar, Rajat Mudgal, Debabrata Sircar, Pravindra Kumar, Shailly Tomar","doi":"10.1002/1873-3468.70054","DOIUrl":"https://doi.org/10.1002/1873-3468.70054","url":null,"abstract":"Chikungunya (CHIKV) and dengue (DENV) viruses pose a public health risk and lack antiviral treatments. Structure-based molecular docking of a natural MTase substrates library identified herbacetin (HC) and caffeic acid phenethyl ester (CAPE) as potential CHIKV nsP1 and DENV NS5 MTase inhibitors. Binding affinities and MTase inhibition were confirmed using purified proteins. The crystal structure of DENV 3 NS5 MTase and CAPE complex revealed CAPE binding at viral RNA capping sites. Interestingly, HC and CAPE depleted polyamines crucial for RNA virus replication and decreased viral titer with IC50 values of ~ 13.44 and ~ 0.57 μm against CHIKV, and ~ 7.24 and ~ 1.01 μm against DENV 3, respectively. Polyamine addition did not reverse the antiviral effects, suggesting a dual inhibition mechanism. Impact statement This study reveals the antiviral potential of natural small molecules, Herbacetin (HC) and Caffeic acid phenethyl ester (CAPE) against Dengue and Chikungunya viruses. The molecules deplete polyamine levels and directly inhibit viral methyltransferases. This study opens new avenues for developing antiviral strategies that target both host factors and viral components.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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