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Structural insights into an engineered feruloyl esterase with improved MHET degrading properties 结构洞察工程阿魏酰酯酶与改进的MHET降解性能。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-03-08 DOI: 10.1002/1873-3468.70322
Panagiota Karampa, Konstantinos Makryniotis, Theofani-Iosifina Sousani, Evangelos Topakas, Vangelis Daskalakis, Maria Dimarogona
{"title":"Structural insights into an engineered feruloyl esterase with improved MHET degrading properties","authors":"Panagiota Karampa,&nbsp;Konstantinos Makryniotis,&nbsp;Theofani-Iosifina Sousani,&nbsp;Evangelos Topakas,&nbsp;Vangelis Daskalakis,&nbsp;Maria Dimarogona","doi":"10.1002/1873-3468.70322","DOIUrl":"10.1002/1873-3468.70322","url":null,"abstract":"<p>Mono(2-hydroxyethyl) terephthalate (MHET) esterases (MHETases) are enzymes implicated in polyethylene terephthalate (PET) biodegradation. The present study elucidates the structural determinants that result in increased MHET degradation by a feruloyl esterase, which has been engineered to resemble the MHETase active site. The crystal structures of the variant in apo- and benzoic acid bound states reveal the changes induced by the introduced mutation, specifically the formation of a hydrogen bond and a <i>trans</i> to <i>cis</i> isomerization of a peptide bond in the vicinity of the catalytic site. Molecular dynamics simulations demonstrate the stabilization of the loop harboring the engineered residue, as well as an expansion of the substrate binding cleft, which would facilitate accommodation of a broader variety of substrates, indicative of a promiscuous biocatalyst.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2729-2743"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Plasmodium falciparum ring-infected erythrocyte surface antigen 3 (PfRESA3) is a cytoskeleton-interacting protein and potential co-chaperone 恶性疟原虫环感染红细胞表面抗原3 （PfRESA3）是一种细胞骨架相互作用蛋白和潜在的共伴侣蛋白。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-04-12 DOI: 10.1002/1873-3468.70340
Nipa Rani Mallick, Welka Sahu, Deepak Kumar Ojha, Shivashis Mund, Aleena Das, Ankit Kumar Pati, Selvakumar Elangovan, K Sony Reddy
{"title":"Plasmodium falciparum ring-infected erythrocyte surface antigen 3 (PfRESA3) is a cytoskeleton-interacting protein and potential co-chaperone","authors":"Nipa Rani Mallick,&nbsp;Welka Sahu,&nbsp;Deepak Kumar Ojha,&nbsp;Shivashis Mund,&nbsp;Aleena Das,&nbsp;Ankit Kumar Pati,&nbsp;Selvakumar Elangovan,&nbsp;K Sony Reddy","doi":"10.1002/1873-3468.70340","DOIUrl":"10.1002/1873-3468.70340","url":null,"abstract":"<p><i>Plasmodium falciparum</i> exports proteins into host erythrocytes for survival, but the roles of many of these proteins remain unexplored. Here, we used recombinant protein constructs and antibodies corresponding to <i>Plasmodium falciparum</i> ring-infected erythrocyte surface antigen-3 (PfRESA3) to identify it as a dense granule merozoite protein exported early to the inner erythrocyte membrane, where it associates with the cytoskeleton. Constructs lacking the J domain bound inside-out vesicles, implicating PRESAN and DnaJ-X in cytoskeletal interactions. Recombinant PfRESA3 constructs stimulated the ATPase activity of human HsHSPA8 and enhanced malate dehydrogenase (MDH) refolding. However, truncated PfRESA3 constructs did not significantly enhance MDH refolding by HsHSPA8. These findings suggest PfRESA3 modulates host HsHSPA8 to support cytoskeletal remodeling/parasite protein folding early in infection.</p><p>\u0000 \u0000 </p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2744-2764"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671560","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
Calpain small subunit homodimerization is robust and calcium-independent 钙蛋白酶小亚基同二聚化是稳健的和不依赖钙的。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-03-08 DOI: 10.1002/1873-3468.70321
Nesha May O. Andoy, Trina Dykstra-MacPherson, Mathias A. Bell, Peter L. Davies, Ruby May A. Sullan
{"title":"Calpain small subunit homodimerization is robust and calcium-independent","authors":"Nesha May O. Andoy,&nbsp;Trina Dykstra-MacPherson,&nbsp;Mathias A. Bell,&nbsp;Peter L. Davies,&nbsp;Ruby May A. Sullan","doi":"10.1002/1873-3468.70321","DOIUrl":"10.1002/1873-3468.70321","url":null,"abstract":"<p>Calpains dimerize via penta-EF-hand (PEF) domains, but their mechanical stability and kinetics remain incompletely characterized. Here, we used single-molecule force spectroscopy on an EGFP-tagged calpain small subunit PEF (CAPNS1-PEF) homodimer to quantify dissociation mechanics. Across retraction speeds of 0.2–10 μm/s, homodimer rupture required large forces (&gt; 300 pN). Rupture forces and force-induced unfolding did not change when Ca<sup>2+</sup> was removed, suggesting Ca<sup>2+</sup>-independent mechanics, consistent with crystal structures showing minimal Ca<sup>2+</sup>-induced conformational changes in the PEF domain. Together, these results indicate that EF-hands in the CAPNS1 homodimer function primarily as structural elements within a mechanically robust, Ca<sup>2+</sup>-insensitive dimerization scaffold.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2777-2786"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Unstructured but dangerous—the emerging roles of intrinsically disordered protein regions in bacterial pathogenesis 非结构化但危险——内在无序的蛋白质区域在细菌发病机制中的新作用。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-05-24 DOI: 10.1002/1873-3468.70368
Diego Forni, Rachele Cagliani, Manuela Sironi
{"title":"Unstructured but dangerous—the emerging roles of intrinsically disordered protein regions in bacterial pathogenesis","authors":"Diego Forni,&nbsp;Rachele Cagliani,&nbsp;Manuela Sironi","doi":"10.1002/1873-3468.70368","DOIUrl":"10.1002/1873-3468.70368","url":null,"abstract":"<p>Intrinsically disordered regions (IDRs) constitute a substantial portion of eukaryotic proteomes but are less prevalent in prokaryotes. Nevertheless, accumulating evidence reveals that IDRs play crucial roles in bacterial virulence, niche adaptation, and host interactions. In this review, we focus on human bacterial pathogens and discuss recent advances in understanding the distribution, evolution, and functional characterization of IDRs. We begin by briefly summarizing their biological properties, conformational ensembles, and representation within bacterial proteomes. We then highlight the diverse mechanisms through which bacterial IDRs interact with and manipulate host cell machineries. These include hijacking host pathways, mediating protein–protein interactions, sensing nutrients and environmental cues, accommodating short linear motifs that mimic eukaryotic signaling elements, and sequestering antimicrobial peptides. Finally, we examine current knowledge and outstanding questions concerning the evolution and antigenicity of bacterial IDRs. Drawing on recent research advances, we provide a focused and accessible overview on how IDRs contribute to the shaping of host–bacteria interactions.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2695-2715"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148014175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Valosin-containing protein counteracts ATP-driven dissolution of FUS condensates through its ATPase activity in vitro 含缬草苷蛋白通过其atp酶活性在体外抵消atp驱动的FUS凝聚物溶解。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-03-16 DOI: 10.1002/1873-3468.70328
Hitomi Kimura, Shin-ichi Tate, Kyota Yasuda
{"title":"Valosin-containing protein counteracts ATP-driven dissolution of FUS condensates through its ATPase activity in vitro","authors":"Hitomi Kimura,&nbsp;Shin-ichi Tate,&nbsp;Kyota Yasuda","doi":"10.1002/1873-3468.70328","DOIUrl":"10.1002/1873-3468.70328","url":null,"abstract":"<p>Fused in sarcoma (FUS) forms phase-separated condensates implicated in amyotrophic lateral sclerosis (ALS). Although millimolar ATP concentrations paradoxically dissolve FUS condensates through hydrotropic activity, condensates nevertheless persist in cells, suggesting active regulatory mechanisms. Here, using a reconstituted system, we show that the AAA+ATPase valosin-containing protein (VCP) counteracts ATP-driven dissolution of FUS condensates. VCP preserved both wild-type and ALS-linked P525L condensates under high ATP conditions, and this protection required catalytic ATPase activity rather than stable partitioning into condensates. The effect was abolished by the D2-specific inhibitor ML240. Our findings establish direct biochemical evidence that VCP ATPase activity maintains FUS condensates under high ATP conditions, highlighting ATPase-driven enzymatic control of liquid–liquid phase separation as a potential general principle with implications for neurodegeneration.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2787-2799"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
‘Guide and Prejudice’— How Argonautes recognize targets across domains of life 《指南与偏见》——阿尔戈英雄如何识别生活中不同领域的目标。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 Epub Date: 2026-09-08 DOI: 10.1002/1873-3468.70450
Jack P. K. Bravo
{"title":"‘Guide and Prejudice’— How Argonautes recognize targets across domains of life","authors":"Jack P. K. Bravo","doi":"10.1002/1873-3468.70450","DOIUrl":"10.1002/1873-3468.70450","url":null,"abstract":"<p>Argonaute proteins mediate RNA interference in eukaryotes and nucleic-acid defence in prokaryotes. Although these systems operate in distinct biological contexts and produce diverse downstream outcomes, they share a conserved structural architecture and mechanism of guide-dependent target recognition. Here, we argue that Argonautes function as programmable surveillance platforms that kinetically sample nucleic acids, engage targets through sequential pairing and conformational checkpoints, and couple recognition to functional outputs through regulated structural transitions. Rather than representing distinct recognition mechanisms, the diverse targeting behaviours observed across Argonaute families reflect different implementations of this shared framework, in which guide biogenesis, target accessibility, pairing requirements and effector coupling are weighted differently according to biological context. Viewing Argonautes through this common operational logic reconciles apparent differences in specificity, mismatch tolerance and target selection across systems, while providing a unified conceptual framework for understanding their evolution and guiding the engineering of programmable nucleic-acid recognition technologies.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 18","pages":"2686-2694"},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Lysyl oxidase (LOX)-mediated remodeling of the extracellular matrix. 赖氨酸氧化酶（LOX）介导的细胞外基质重塑。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-28 DOI: 10.1002/1873-3468.70472
Fernando Rodríguez-Pascual, Marta Navarro-Gutiérrez, Verónica Romero-Albillo, Raquel Jiménez-Sánchez
{"title":"Lysyl oxidase (LOX)-mediated remodeling of the extracellular matrix.","authors":"Fernando Rodríguez-Pascual, Marta Navarro-Gutiérrez, Verónica Romero-Albillo, Raquel Jiménez-Sánchez","doi":"10.1002/1873-3468.70472","DOIUrl":"https://doi.org/10.1002/1873-3468.70472","url":null,"abstract":"<p><p>The lysyl oxidase (LOX) family of enzymes drives extracellular matrix remodeling by oxidizing collagen, elastin, and fibronectin, promoting covalent cross-link formation. This activity regulates tissue architecture and mechanical properties, while its dysregulation contributes to fibrosis, cardiovascular disease, glaucoma, connective tissue disorders, and cancer.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069398","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
From timekeeping to divisions-Molecular links between circadian rhythms and cell cycle. 从计时到分裂——昼夜节律和细胞周期之间的分子联系。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-26 DOI: 10.1002/1873-3468.70477
Sevde Goker, Junghyun Lee, Attila Csikász-Nagy, Christian I Hong
{"title":"From timekeeping to divisions-Molecular links between circadian rhythms and cell cycle.","authors":"Sevde Goker, Junghyun Lee, Attila Csikász-Nagy, Christian I Hong","doi":"10.1002/1873-3468.70477","DOIUrl":"https://doi.org/10.1002/1873-3468.70477","url":null,"abstract":"<p><p>Circadian rhythms and the cell cycle are two fundamental biological oscillators. They are linked through molecular mechanisms creating coupled oscillators where the outcomes of this coupling depend on numerous factors, such as the directionality of coupling (i.e., unidirectional vs. bidirectional), periods of the two oscillators, and the number and strength of connections. In this review, we provide a general overview of the links between circadian rhythms and the cell cycle and discuss potential implications of this connection in stem cell proliferation and differentiation of mammalian cells.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059102","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
Smaller is better: nanobodies meet NMR. 越小越好：纳米体符合核磁共振。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-25 DOI: 10.1002/1873-3468.70473
Oleg Y Dmitriev
{"title":"Smaller is better: nanobodies meet NMR.","authors":"Oleg Y Dmitriev","doi":"10.1002/1873-3468.70473","DOIUrl":"https://doi.org/10.1002/1873-3468.70473","url":null,"abstract":"<p><p>Nanobodies, the single-domain antigen-binding fragments derived from camelid heavy chain antibodies, have emerged as powerful tools in structural biology. Their small size, high stability, and ability to bind with exceptional specificity make them ideal for applications in nuclear magnetic resonance (NMR) spectroscopy. In protein NMR, nanobodies can serve as chaperones to stabilize flexible regions, reduce conformational heterogeneity, and enhance spectral quality. They facilitate the study of challenging targets such as membrane proteins, large complexes, and intrinsically disordered proteins by improving solubility and enabling selective labeling strategies. Furthermore, nanobody-assisted NMR spectroscopy provides unique opportunities for probing dynamic interactions and conformational states under near-physiological conditions. This review summarizes recent advances in nanobody engineering for NMR studies, including the synthetic nanobodies, highlights the nanobodies' role in overcoming size and stability limitations, and discusses future directions for integrating nanobodies into emerging NMR methodologies, with an emphasis on protein dynamics and protein-protein interactions in the context of drug discovery.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037244","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
Membrane composition and thermodynamic identity as boundaries of life for synthetic cell research. 膜组成和热力学同一性作为合成细胞研究的生命边界。
IF 3 4区 生物学
FEBS Letters Pub Date : 2026-09-25 DOI: 10.1002/1873-3468.70476
Caterina Presutti, Bert Poolman
{"title":"Membrane composition and thermodynamic identity as boundaries of life for synthetic cell research.","authors":"Caterina Presutti, Bert Poolman","doi":"10.1002/1873-3468.70476","DOIUrl":"https://doi.org/10.1002/1873-3468.70476","url":null,"abstract":"<p><p>Biological membranes are more than structural boundaries: they are the thermodynamic interfaces that enable living systems to maintain a state far from equilibrium, continuously exchanging matter and energy with their environment. In this review, we explore three interconnected themes. First, we examine the biochemical composition of cell membranes, with particular focus on Escherichia coli, including lipid diversity, membrane asymmetry, and homeoviscous adaptation. Second, we reframe the membrane as the physical representation of the Markov blanket, the statistical boundary separating internal from external states, and discuss how biological systems minimize free energy to maintain homeostasis. Third, we evaluate synthetic cell research strategies for reconstructing life-like systems, highlighting how out-of-equilibrium approaches, based on selective membrane transport coupled to metabolic networks, may recapitulate the thermodynamic identity of living cells.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037317","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
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