The FEBS journal最新文献

{"title":"Catalysis and allostery in bacterial ATP phosphoribosyltransferases.","authors":"Lillian G Bates, Rafael G da Silva","doi":"10.1111/febs.70769","DOIUrl":"https://doi.org/10.1111/febs.70769","url":null,"abstract":"<p><p>ATP phosphoribosyltransferase (ATPPRT) catalyses the first reaction of L-histidine biosynthesis: the condensation of ATP and 5-phospho-α-d-ribose 1-pyrophosphate to form N¹-(5-phospho-β-d-ribosyl)-ATP with the release of inorganic pyrophosphate. L-Histidine allosterically inhibits ATPPRT as a mechanism to regulate this energy-intensive pathway in histidine-synthesising organisms, such as bacteria, archaea and plants. Absent in humans and essential in many disease-causing bacteria, such as Mycobacterium tuberculosis and Acinetobacter baumannii, ATPPRT is a promising drug target for novel antibiotic development. Furthermore, ATPPRT is a target of synthetic biology efforts to maximise L-histidine production in bacteria. Here we provide a brief overview of allosteric concepts and review the structure, catalysis and allosteric mechanism of bacterial ATPPRTs, which exist in two forms in nature, a long and a short form. We highlight recent findings on ATPPRT catalysis, allosteric regulation, inhibition and activation, discuss open questions in the field, and possible industrial and biomedical applications.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229568","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}

{"title":"Correction to \"Distinct and potent vitamin D hydroxylation activity acquired by the CYP3A4 I301T single amino acid substitution causes type 3 rickets\".","authors":"","doi":"10.1111/febs.70771","DOIUrl":"https://doi.org/10.1111/febs.70771","url":null,"abstract":"","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229591","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}

{"title":"The different roles of the eS31 ribosomal protein in ribosome biogenesis and translation in Saccharomyces cerevisiae","authors":"Eduardo Villalobo,&nbsp;Jesús de la Cruz","doi":"10.1111/febs.70580","DOIUrl":"10.1111/febs.70580","url":null,"abstract":"<p>Many ribosomal proteins in yeast possess extensions that protrude from their globular cores to facilitate rRNA folding, ribosome assembly, and translation. Previous work established that the eukaryote-specific N-terminal domain of eS31 harbors a nuclear localization signal; its deletion impairs growth and 40S biogenesis while inducing ribosomal misreading. Gao <i>et al.,</i> now provide further insights into this extension, identifying a critical cluster of basic residues essential for elongation fidelity. Furthermore, they demonstrate that full-domain deletion compromises termination through a ‘<i>trans</i>-acting disruption’ process requiring wild-type eS31. These findings highlight novel mechanisms underlying ribosome heterogeneity and specialization.</p><p>Comment on: https://doi.org/10.1111/febs.70510</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6016-6021"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848222","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}

{"title":"ACTR3 enhances the hyperproliferation of psoriatic keratinocytes by activating the TAK1-MK2-HSP27 pathway","authors":"Jianxiao Xing,&nbsp;Junqin Li,&nbsp;Ying Wang,&nbsp;Yanyang Liang,&nbsp;Yuanjun Yao,&nbsp;Yali He,&nbsp;Xuping Niu,&nbsp;Kaiming Zhang","doi":"10.1111/febs.70558","DOIUrl":"10.1111/febs.70558","url":null,"abstract":"<p>Psoriasis is a chronic immune-mediated skin disorder characterised by abnormal keratinocyte proliferation and cutaneous inflammation. ACTR3 (actin-associated protein 3) is significantly overexpressed in both cutaneous malignant tumours and psoriatic keratinocytes, and is recognised as a potential key nodal molecule linking tumours to inflammatory skin conditions. Lysine 2-hydroxyisobutyrylation (Khib)—a critical post-translational modification—exerts regulatory effects on the pathogenesis of various diseases; however, its specific role in psoriasis pathogenesis remains elusive. In this study, we demonstrated that elevated ACTR3 expression in cutaneous tumours and psoriasis promotes abnormal keratinocyte proliferation in psoriasis. Khib-modified protein profiles in epidermal tissues from psoriatic patients and healthy controls were analysed, leading to the identification of ACTR3 as a differential target protein. Results showed that Khib modification levels at the K42 site of ACTR3 were significantly reduced in lesional tissues from psoriatic patients and imiquimod (IMQ)-induced psoriatic mice. Further validation using ACTR3 K42A mutation experiments confirmed that decreased Khib modification at this site exacerbates IMQ-induced psoriatic inflammation and keratinocyte proliferation. Deacetylases Sirt1 and HDAC1 were found to reduce ACTR3 Khib modification levels, thereby regulating ACTR3 expression and subsequent keratinocyte (KC) proliferation. Additionally, signalling pathway analysis revealed that downregulated K42-Khib modification of ACTR3 enhances keratinocyte proliferation by activating the TAK1-MK2-HSP27 pathway. Notably, TAK1 antagonists effectively reversed abnormal keratinocyte proliferation and psoriatic inflammation induced by the ACTR3 K42A mutation. This study elucidates that reduced Khib modification at the ACTR3 K42 locus promotes keratinocyte proliferation via regulation of the TAK1-MK2-HSP27 signalling pathway, offering a previously undescribed molecular insight into psoriasis pathogenesis.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6114-6136"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848169","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}

{"title":"Functional emergence driven by structural evolution of the DSBH domain in Fe2+ and α-ketoglutarate-dependent family","authors":"Siqi Yang,&nbsp;Jixiang Xing,&nbsp;Lingling Bao,&nbsp;Jiafu Cui,&nbsp;Dongyang Liu,&nbsp;Shaoran Wen,&nbsp;Shuhua Xu,&nbsp;Yongchun Zuo","doi":"10.1111/febs.70565","DOIUrl":"10.1111/febs.70565","url":null,"abstract":"<p>Ten-eleven translocation (TET), AlkB homolog (ALKBH), and histone lysine demethylase (KDM) proteins belong to the 2-oxoglutarate (2OG) and ferrous iron-dependent oxygenases, which catalyze substrates spanning the entire central dogma (DNA–RNA–Protein). It serves as a model for understanding how functional diversity is shaped by structural changes within the central dogma. The evolutionary characteristics of the core catalytic domain double-stranded β-helix (DSBH) are the main reasons for their specific substrate recognition ability. Nonetheless, the structural biological explanations remain ambiguous. Here, we constructed the sequence evolutionary tree of the full-length and DSBH catalytic domains from seven prevalent mammalian species. The DSBH domain evolutionary trajectory was generated by multispecies structure fitting and mapping. Taking humans as a reference, the relationships among the three subfamilies, KDM, ALKBH, and TET, were depicted. In conjunction with the evolutionary tree and domain map, this method analyzed the emergence and extinction of α-helix and β-sheet structures and length variations in pivotal regions to ascertain the structural history of DSBH domains across subfamilies. Furthermore, reduced amino acid analysis and prospective mapping were utilized to investigate the correlation between the structural progression and functional assessment of the DSBH structure. A new perspective has arisen, highlighting variations in the proregion of the DSBH domain as essential for its particular substrate recognition function, as this domain determines the binding conditions for protein substrates. This provides a new angle for understanding the evolution of proteins from simple structures to complex functions and leads to new advances for the bioengineering field.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6176-6192"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793648","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}

{"title":"From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system","authors":"Lukas Meisinger,&nbsp;Alice Wiedmann,&nbsp;Rayan Hassan M. Elshikhidriss,&nbsp;Thomas Brunner","doi":"10.1111/febs.70589","DOIUrl":"10.1111/febs.70589","url":null,"abstract":"<p>The nuclear receptor NR5A2 (Liver Receptor Homolog-1, LRH-1) has been well characterized in tissues of endodermal origin for the transcriptional control of development, metabolism, and steroidogenesis. In this minireview, we discuss the so far underappreciated expression and role of LRH-1 in hematopoietic cells. We further highlight how deregulation of LRH-1 may contribute to the pathogenesis of leukemia and immune cell-mediated diseases, and how targeting LRH-1 can be employed in immune cell-targeted therapies. Given that LRH-1 expression and function are highly tissue-specific, we further discuss how these contextual differences may be exploited to achieve therapeutic selectivity, especially focusing on the myeloid and T cell lineage. Although current evidence for LRH-1 functions in these immune cells is yet limited, its established role in the transcriptional regulation of development, differentiation, metabolism, proliferation, and cytokine expression of hematopoietic cells suggests a substantial and largely unexploited potential for therapeutic applications in leukemia and immunopathological diseases.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"5996-6010"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936010","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}

{"title":"Fungal oxyluciferin is recycled by caffeylpyruvate hydrolases","authors":"Alena K. Malyshevskaia,&nbsp;Aleksei D. Barykin,&nbsp;Daria A. Kisilichuk,&nbsp;Tatiana V. Chepurnykh,&nbsp;Ekaterina S. Shakhova,&nbsp;Maxim M. Perfilov,&nbsp;Olga A. Belozerova,&nbsp;Kseniia A. Palkina,&nbsp;Nadezhda M. Markina,&nbsp;Caio K. Zamuner,&nbsp;Douglas M. M. Soares,&nbsp;Renata I. Zagitova,&nbsp;Zinaida M. Kaskova,&nbsp;Cassius V. Stevani,&nbsp;Andrey Y. Gorokhovatsky,&nbsp;Alexander S. Mishin,&nbsp;Karen S. Sarkisyan,&nbsp;Ilia V. Yampolsky","doi":"10.1111/febs.70555","DOIUrl":"10.1111/febs.70555","url":null,"abstract":"<p>In the fungal bioluminescence pathway, caffeylpyruvate (fungal oxyluciferin) is recycled to caffeic and pyruvic acids through hydrolysis. The reaction is thought to be catalysed by a putative caffeylpyruvate hydrolase, possibly encoded by the <i>cph</i> gene, a member of the biosynthetic gene cluster encoding bioluminescence. Here, we experimentally confirmed the role of CPH as caffeylpyruvate hydrolase <i>in vitro</i> and <i>in vivo</i>. We show that oxyluciferin is an inhibitor of the bioluminescence reaction and that CPH orthologues from various bioluminescent fungi differ in their ability to hydrolyse oxyluciferin. This suggests a possible role of caffeylpyruvate hydrolases in bioluminescent fungi and highlights CPH as a target for directed evolution to develop autoluminescent reporter tools.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6038-6050"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978382","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}

{"title":"Prebiotic aqueous reactions catalyzed by native nickel without hydrogen","authors":"Carolina Garcia Garcia,&nbsp;Max Brabender,&nbsp;William F. Martin","doi":"10.1111/febs.70556","DOIUrl":"10.1111/febs.70556","url":null,"abstract":"<p>Compared to iron, nickel is comparatively rare as a transition metal in enzymes. However, it is essential in several enzymes of carbon and energy metabolism in acetogens (bacteria) and methanogens (archaea), which use the acetyl-CoA pathway of H₂-dependent CO₂ fixation. Nickel containing enzymes of acetogens and methanogens include FeNi hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA synthase and, in methanogens, methyl-CoM reductase in the last step of methane synthesis. Several lines of evidence implicate the acetyl-CoA pathway as the most ancient pathway of CO₂ fixation, most notably recent findings that the overall reaction of the enzymatic pathway from H₂ (<i>E</i>₀′ = −414 mV) and CO₂ to pyruvate can be replaced by Ni⁰ alone in water as the lone catalyst. Here, we studied Ni⁰ as a catalyst and reductant for nonenzymatic redox reactions that require only a mild reductant, as the midpoint potential of Ni⁰ oxidation to Ni²⁺ is <i>E</i>₀′ = −260 mV. We showed that Ni⁰ in water can convert 2-oxo acids to 2-hydroxy acids and, in the presence of NH₃, to amino acids at 25–100 °C without the addition of H₂, and that it functions as a catalyst and reductant for the fumarate reductase reaction. The findings expand the repertoire of ancient metabolic reactions that Ni⁰ can catalyze without proteins, cofactors, or sulfur, shedding light on the broad catalytic activity and substrate specificity of Ni⁰ at metabolic origin.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6100-6113"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719216","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}

{"title":"Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP/TAZ transcriptional cofactors in hepatocytes","authors":"Brenda Selene Torres-Ortiz,&nbsp;Daniel Pérez-Calixto,&nbsp;Jorge Carretero-Ortega,&nbsp;Aida Gabriela Guzman-López,&nbsp;Diana Cristina Pinto-Dueñas,&nbsp;Mariana Hernández-Juárez,&nbsp;Alejandra Jiménez-Escobar,&nbsp;Adriana Rodríguez-Hernández,&nbsp;Beatriz Díaz-Bello,&nbsp;Nathalia Serna-Márquez,&nbsp;Miguel Ángel Peña-Rico,&nbsp;Laura Gómez-Romero,&nbsp;Francisco Gabriel Vázquez-Cuevas,&nbsp;Genaro Vázquez-Victorio","doi":"10.1111/febs.70570","DOIUrl":"10.1111/febs.70570","url":null,"abstract":"<p>During liver fibrosis, hepatocytes respond to progressive increases in tissue stiffness by undergoing cytoskeletal reorganisation. This has important consequences such as immune cell infiltration, mainly triggered by the activation of YAP and TAZ proteins. However, other proteins that respond to mechanical modifications remain poorly characterised; in particular, the myocardin-related transcription factors A and B (MRTFs). Here, we referred to these four proteins as mechanical responsive transcriptional cofactors (MRTcoF). We analysed the regulation of MRTcoF proteins in fibrotic livers induced by carbon tetrachloride (CCl₄) and observed that MRTcoF were differentially regulated during liver fibrosis, predominantly in hepatocytes. Transcriptome analysis suggested that fatty acid and glucose metabolisms, cell proliferation and signalling pathways were regulated by transcriptional enhanced associate domain (TEAD)- and serum response factor (SRF)-transcriptional programmes in CCl₄-treated livers. Then, we evaluated the protein expression levels of MRTcoF in primary hepatocytes (PH) cultured on tissue culture petri dishes (TCPD). After culture, we observed upregulation of MRTcoF, and downregulation of TAZ after protein increase. Interestingly, despite the increase in MRTFB protein levels, no accumulation of MRTFB was detected in the nucleus. Culture on soft polyacrylamide hydrogels (PAA HGs) attenuated the activation of MRTcoF, having specific implications in the transcriptional regulation of target genes. In contrast, pharmacological inhibition of MRTcoF was not sufficient to halt transcriptional regulation. In summary, a progressive increase of stiffness activates MRTcoF transcriptional complexes in hepatocytes, suggesting a key role of mechano-transduction during liver fibrosis.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6230-6252"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825153","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}

{"title":"On the other side of the membrane: A new role for a luminal protein in the cytoplasm","authors":"Erik Snapp","doi":"10.1111/febs.70586","DOIUrl":"10.1111/febs.70586","url":null,"abstract":"<p>Proteins annotated as localizing inside membrane-bound organelles are accepted as residing there. Thus, encountering a mitochondrial cytochrome in the cytoplasm would be unexpected. Yet, a mitochondrial cytochrome does relocalize to the cytoplasm during apoptotic cell death. In fact, a growing list of annotated luminal proteins has demonstrable cytoplasmic functions. It is with this perspective of bi-compartmental proteins that I encourage you to read the new study from Zhu and Fu in this issue of <i>The FEBS Journal</i>. The authors investigate how stress inside the ER lumen influences cytoplasmic energy regulation and uncover a surprising mechanism in fission yeast.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 20","pages":"6011-6015"},"PeriodicalIF":4.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966339","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}