FEBS Letters最新文献

{"title":"The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron–sulfur cluster maturation of the mitoribosome assembly factor Rsm22","authors":"Ulrich Mühlenhoff,&nbsp;Dominik Trauth,&nbsp;Weronika Śliwińska,&nbsp;Linda Boss,&nbsp;Roland Lill","doi":"10.1002/1873-3468.70129","DOIUrl":"10.1002/1873-3468.70129","url":null,"abstract":"<p>Mitochondria contain the bacteria-inherited iron–sulfur cluster assembly (ISC) machinery to generate cellular iron–sulfur (Fe/S) proteins. Mutations in human <i>ISC</i> genes cause severe disorders with a broad clinical spectrum and are associated with strong defects in mitochondrial Fe/S proteins, including respiratory complexes I–III. For unknown reasons, complex IV (aka cytochrome <i>c</i> oxidase), a non-Fe/S, heme-containing enzyme, is severely affected. Using yeast as a model, we show that depletion of Rsm22, the counterpart of the human mitoribosome assembly factor METTL17, phenocopies the defects observed upon impairing late-acting ISC proteins, that is, diminished activities of mitoribosomal translation and respiratory complexes III and IV. Rsm22 binds Fe/S clusters <i>in vivo</i>, thereby satisfactorily explaining the defect of respiratory complex IV in ISC-deficient cells, because this complex contains three mitochondrial DNA-encoded subunits.</p><p>\u0000 </p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 16","pages":"2301-2317"},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793863","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}

{"title":"Structural basis of a GatC ortholog transporter in the bacterial phosphotransferase system","authors":"Yutaro S. Takahashi,&nbsp;Hidetaka Kohga,&nbsp;Min Fey Chek,&nbsp;Kotomi Yamamoto,&nbsp;Jun F. Takahashi,&nbsp;Hideki Shigematsu,&nbsp;Yoshiki Tanaka,&nbsp;Muneyoshi Ichikawa,&nbsp;Ryoji Miyazaki,&nbsp;Toshio Hakoshima,&nbsp;Tomoya Tsukazaki","doi":"10.1002/1873-3468.70135","DOIUrl":"10.1002/1873-3468.70135","url":null,"abstract":"<p>The bacterial phosphotransferase system (PTS) mediates the uptake of specific carbohydrates via IIC transporters. Here, we report the crystal and cryo-electron microscopy (cryo-EM) structures of <i>Leminorella grimontii</i> galactitol-specific PTS enzyme IIC component (LgGatC), which is implicated in D-xylose uptake and belongs to the ascorbate–galactitol (AG) superfamily of IIC proteins. These structures, determined in the presence and absence of D-xylose, capture the transporter in an outward-facing conformation. A homology model of an inward-facing state, constructed based on these structures, supports an elevator-like transport mechanism. These findings provide structural insights into substrate recognition by GatC and offer a framework for understanding sugar transport in PTS IIC proteins.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 16","pages":"2377-2387"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894169","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}

{"title":"Functional role and folding properties of the glucan-binding domain of oral bacterial glucansucrase","authors":"Hideyuki Komatsu,&nbsp;Takayuki Sadakane,&nbsp;Yudai Murata,&nbsp;Junichi Taira,&nbsp;Hiroshi Sakamoto,&nbsp;Takao Kodama","doi":"10.1002/1873-3468.70128","DOIUrl":"10.1002/1873-3468.70128","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>A <i>Streptococcus sobrinus</i> glucansucrase (i.e., glucosyltransferase-I) elongates α-1, 3-linked glucose chains at pre-existing branch points of dextran, and its activity is enhanced by primer dextran. The glucansucrase contains a catalytic domain and a glucan-binding domain (GBd) with six tandem repeats. We here examined the role of GBd in the glucansucrase, focusing on its impact on enzymatic activity, dextran binding, and structural stability. By generating seven deletion mutants and a circularly permuted protein, our research demonstrates that the first four tandem repeats in the GBd and proper domain orientation are required for efficient glucosyl transfer. Moreover, characterization of circular dichroism and thermal unfolding indicated that glucosyl transfer efficiency is linked to cooperative interdomain folding. These findings highlight the importance of interdomain allostery in optimizing glucansucrase function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>Our research on the role of the glucan-binding domain in <i>Streptococcus sobrinus</i> glucansucrase revealed that glucosyl transfer efficiency is linked to cooperative interdomain folding. The finding highlights the importance of interdomain allostery in optimizing glucansucrase function and also suggests potential targets for inhibiting bacterial biofilm formation.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 16","pages":"2388-2402"},"PeriodicalIF":3.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768564","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}

{"title":"RETRACTION: Silencing SARS-CoV Spike Protein Expression in Cultured Cells by RNA Interference","authors":"","doi":"10.1002/1873-3468.70127","DOIUrl":"10.1002/1873-3468.70127","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>Y. Zhang</span>, <span>T. Li</span>, <span>L. Fu</span>, <span>C. Yu</span>, <span>Y. Li</span>, <span>X. Xu</span>, <span>Y. Wang</span>, <span>H. Ning</span>, <span>S. Zhang</span>, <span>W. Chen</span>, <span>L.A. Babiuk</span>, and <span>Z. Chang</span>, “ <span>Silencing SARS-CoV Spike Protein Expression in Cultured Cells by RNA Interference</span>,” <i>FEBS Letters</i> <span>560</span>, nos. <span>1-3</span> (<span>2004</span>): <span>141</span>-<span>146</span>, https://doi.org/10.1016/S0014-5793(04)00087-0.\u0000 </p><p>The above article, published online on 4 February 2004 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to duplications within Figures 3 and 6, as well as evidence of splicing in Figure 5. The authors were contacted and the original data were requested, but they were unable to provide those data due to the length of time since the publication. Therefore, the article must be retracted due to the editor's loss of confidence in the validity of the reported conclusions. All co-authors agree with the decision to retract with the exception of Yuanjiang Zhang and Wei Chen, who are unavailable for comment.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768565","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}

{"title":"Goodbye flat lymphoma biology.","authors":"Carla Faria, Cèlia Dobaño-López, Patricia Pérez-Galán, Christine Bezombes","doi":"10.1002/1873-3468.70114","DOIUrl":"https://doi.org/10.1002/1873-3468.70114","url":null,"abstract":"<p><p>B-cell lymphomas grow in aggregates, closely interacting with specific physical elements and cellular environments. While 2D culture systems have long been the standard in the field, current methodologies aim to better replicate lymphoma biology and its microenvironment in 3D. Significant progress has been made since the first 3D lymphoma cell line culture was developed in 2012. Subsequent advances in both cell line and patient-derived systems have incorporated key physical and cellular microenvironmental components. This Review compiles the relevant 3D non-Hodgkin lymphoma models available, outlining their main features, strengths, and limitations. Additionally, we highlight the critical gaps that must be addressed to develop robust, multiplexed, patient-derived B-cell lymphoma systems, which can serve as reliable avatars alongside clinical trials and contribute to the principles of the 3Rs in animal research. Impact statement In the last few years new B-cell lymphoma 3D models have emerged, with a special emphasis on patient-derived models. These systems are fundamental tools for precision medicine. This review provides translational researchers and clinician scientists with an excellent overview of these novel tools with their strong and weak points.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752751","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}

{"title":"Neutrophil deficiency increases T cell numbers at the site of tissue injury in mice","authors":"Hajnalka Halász,&nbsp;Albert Bálint Papp,&nbsp;Lukács Sándor Lesinszki,&nbsp;Attila Mócsai,&nbsp;Tamás Varga,&nbsp;László Nagy,&nbsp;Péter Gogolák","doi":"10.1002/1873-3468.70126","DOIUrl":"10.1002/1873-3468.70126","url":null,"abstract":"<p>During the investigation of muscle injury and regeneration in neutrophil-deficient mice, we observed unexpected changes in the cellular composition of tissue-infiltrating inflammatory cells. Neutrophil deficiency led to reduced macrophage infiltration and a striking increase in nonconventional CD4⁻ CD8⁻ (double-negative) αβ and γδ T cell numbers, peaking at Day 3 postinjury. In exploring the underlying mechanisms, we identified previously unrecognized cellular and tissue alterations, including bone marrow erythroid insufficiency and compensatory extramedullary hematopoiesis accompanied by splenomegaly. Using a thioglycolate-induced peritonitis model, we further demonstrated that elevated T-cell numbers reflect a general inflammatory response in neutrophil-deficient mice. Our findings suggest that this model provides a valuable platform for investigating the properties and functions of rare nonconventional T cells in tissue injury and diverse inflammatory conditions.\u0000 </p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2644-2662"},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729021","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}

{"title":"Dendritic cells in focus: mapping functional diversity through technological innovation","authors":"Francesco Andreata,&nbsp;Francesca Granucci,&nbsp;Laura Marongiu","doi":"10.1002/1873-3468.70109","DOIUrl":"10.1002/1873-3468.70109","url":null,"abstract":"&lt;p&gt;Since their initial identification by Ralph Steinman and Zanvil Cohn in the 1970s [&lt;span&gt;[1]&lt;/span&gt;], dendritic cells (DCs) have been established as critical regulators of immune responses. While initially characterized as a relatively homogeneous population of potent antigen-presenting cells responsible for priming naïve T lymphocytes, it is now recognized that DCs comprise a complex and heterogeneous network of subsets. These include conventional DCs (cDC1 and cDC2), plasmacytoid DCs (pDCs), and monocyte-derived inflammatory DCs, each exhibiting distinct developmental origins, surface marker expression, and specialized functional properties. The phenotypic and functional characteristics of DCs are significantly influenced by the tissue microenvironment in which they reside, with DCs in the skin, lung, intestine, lymph nodes, and tumors demonstrating context-specific programs. This remarkable plasticity underscores the role of DCs not only as initiators of immunity but also as dynamic modulators of immune homeostasis, tolerance, and inflammation.&lt;/p&gt;&lt;p&gt;The &lt;i&gt;FEBS Letters&lt;/i&gt; Special Issue ‘Dendritic cells in health and disease’ focuses on recent conceptual and technological advancements that are refining our understanding of DC biology (Fig. 1). The included articles investigate DCs across diverse tissues and disease states, highlighting the translation of technological innovation into novel therapeutic perspectives.&lt;/p&gt;&lt;p&gt;A fundamental aspect of understanding DC identity lies in recognizing that context is a critical determinant of their properties. Whether located within a lymph node or residing in the lung, DCs exhibit adaptability in their morphology, function, and fate. The coordinated action of resident and migratory DCs in lymph nodes, a topic further explored in this issue, illustrates the influence of the spatial and temporal dynamics of immune cell interactions on T-cell activation.&lt;/p&gt;&lt;p&gt;Expanding beyond tissue architecture, the liver provides a relevant example of the intricate relationship between metabolic cues and immune regulation, positioning immunometabolism as a central aspect of DC biology. In their Review, Klaimi &lt;i&gt;et al&lt;/i&gt;. [&lt;span&gt;[2]&lt;/span&gt;] examine hepatic DCs as integrators of dietary, microbial, and metabolic signals. Their work elucidates how these cells modulate their functions to promote either immune tolerance or inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD). By integrating data from animal models and human pathology, they emphasize the liver as a key site of convergence between immune and metabolic regulation, with DCs occupying a pivotal position at this interface.&lt;/p&gt;&lt;p&gt;To further delineate the evolving understanding of DC heterogeneity, this Special Issue features a series of Reviews providing both mechanistic insights and methodological guidance. In their Review, Protti and Spreafico offer a comprehensive guide to the application of single-cell RNA sequencing (scRNA-seq)","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 14","pages":"1967-1970"},"PeriodicalIF":3.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714614","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}

{"title":"The anabolic steroid stanozolol is a potent inhibitor of human MutT homolog 1","authors":"Emma Scaletti Hutchinson,&nbsp;Robert Gustafsson Westergren,&nbsp;Ingrid Almlöf,&nbsp;Ann-Sofie Jemth,&nbsp;Martin Scobie,&nbsp;Ulrika Warpman Berglund,&nbsp;Thomas Helleday,&nbsp;Pål Stenmark","doi":"10.1002/1873-3468.70116","DOIUrl":"10.1002/1873-3468.70116","url":null,"abstract":"<p>Human MutT homolog 1 (hMTH1) removes damaged nucleotides from the nucleotide pool, preventing their incorporation into DNA. Due to its potential as an anticancer drug target, hMTH1 has been the focus of several inhibitor development studies. Unexpectedly, we show that the anabolic steroid stanozolol (Stz) is a potent nanomolar inhibitor of hMTH1. We present the structure of hMTH1 in complex with Stz, which indicates a unique core scaffold that could be exploited for future inhibitor development. Comparison with human protein structures bound with dihydrotestosterone (DHT) shows hMTH1 is entirely unrelated in terms of its structure. As these DHT binding proteins are all involved in steroid regulation, this makes the identification of Stz as a potent hMTH1 inhibitor all the more unusual.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 19","pages":"2790-2801"},"PeriodicalIF":3.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947921","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}

{"title":"Crystal structure of a family II pyrophosphatase from Thermodesulfobacterium commune and factors enabling its high-temperature adaptation","authors":"Saki Maruoka,&nbsp;Takamasa Teramoto,&nbsp;Keiichi Watanabe,&nbsp;Yoshimitsu Kakuta","doi":"10.1002/1873-3468.70124","DOIUrl":"10.1002/1873-3468.70124","url":null,"abstract":"<p>Inorganic pyrophosphatases (PPases) are crucial for energy metabolism and are classified into families with distinct metal ion requirements and structural features. Here, we report the expression, purification, and crystal structure of a thermostable family II PPase from the thermophile <i>Thermodesulfobacterium commune</i> (<i>Tc</i>PPase). <i>Tc</i>PPase, which is optimally activated by Co²⁺ and Mn²⁺, requires both the N- and C-terminal domains for full catalytic activity. Comparative structural analyses with orthologous enzymes from psychrophilic and mesophilic organisms suggest that the thermostability of <i>Tc</i>PPase is attributable to enhanced hydrophobic interactions, increased proline content, dense hydrogen-bonding networks, and additional salt bridges. These findings reveal the molecular basis for the thermal adaptation of family II PPases, providing valuable insights for thermostable enzyme engineering for biotechnological applications.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 15","pages":"2220-2232"},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815196","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}

{"title":"Archaeal protein containing domain of unknown function 2193 undergoes oligomeric reconfiguration upon iron–sulfur cluster binding","authors":"Emily M. Dieter,&nbsp;James Larson,&nbsp;Monika Tokmina-Lukaszewska,&nbsp;Jin Xiong,&nbsp;Jared Green,&nbsp;Yisong Guo,&nbsp;William E. Broderick,&nbsp;Brian Bothner,&nbsp;Joan B. Broderick","doi":"10.1002/1873-3468.70120","DOIUrl":"10.1002/1873-3468.70120","url":null,"abstract":"<p>Methanogenic archaea are particularly rich in iron–sulfur proteins, yet their roles remain largely enigmatic. Here, we characterized a <i>Methanococcus voltae</i> (<i>Mvo</i>) protein from the domain of unknown function (DUF) 2193 family, a group of proteins present primarily in archaea and characterized by a conserved cysteine-rich C-terminal motif. <i>Mvo</i>DUF2193 was heterologously expressed and characterized by a range of spectroscopic and analytical methods. The results demonstrate that <i>Mvo</i>DUF2193 binds a single [4Fe–4S] cluster per subunit and that cluster occupancy regulates the transition from an apo tetramer to a [4Fe–4S] monomeric form. We hypothesize that <i>Mvo</i>DUF2193 serves a regulatory role in the cell, mediated by [Fe–S] cluster binding and changes in oligomeric state.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 16","pages":"2318-2333"},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729020","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}