The FEBS journal最新文献

Transglutaminase-mediated cytokeratin modifications implicated in bile-acid-induced hepatocyte death. 转谷氨酰胺酶介导的细胞角蛋白修饰与胆汁酸诱导的肝细胞死亡有关。

IF 4.2

The FEBS journal Pub Date : 2025-10-12 DOI: 10.1111/febs.70281

Hideki Tatsukawa, Haruka Nakagawa, Chin Mun Yee, Keiko Kuwata, Kiyotaka Hitomi

{"title":"Transglutaminase-mediated cytokeratin modifications implicated in bile-acid-induced hepatocyte death.","authors":"Hideki Tatsukawa, Haruka Nakagawa, Chin Mun Yee, Keiko Kuwata, Kiyotaka Hitomi","doi":"10.1111/febs.70281","DOIUrl":"https://doi.org/10.1111/febs.70281","url":null,"abstract":"Transglutaminases (TGs) are crosslinking enzymes that catalyze the formation of isopeptide bonds between glutamine and lysine residues. They consist of eight isozymes: TG1-TG7 and factor XIIIa. Our previous studies have shown that TG1 and TG2 facilitate hepatic apoptosis, contributing to liver fibrosis, and that their crosslinking substrates-cytokeratin 18 (K18) and cytokeratin 8 (K8)-are also targeted by TGs in a bile-duct-ligation-induced mouse model of liver fibrosis. However, the precise mechanisms by which TGs and keratins contribute to hepatocyte damage remain unclear. This study investigates the molecular mechanisms underlying TG1- and TG2-mediated cell death in hepatocytes exposed to bile acids. HepG2 cells and primary hepatocytes were treated with glycochenodeoxycholic acid (GCDCA), a toxic bile salt elevated in cholestasis. GCDCA-reduced cell viability and induced apoptosis in a dose-dependent manner. Knockdown of K18/K8 or TG1/TG2 by siRNA significantly attenuated GCDCA-induced apoptosis, indicating their contributory roles in hepatocyte injury. GCDCA-treated cells showed increased levels of proteins crosslinked by TG1 and TG2. In vivo analysis using cholestatic model mice also showed elevated high-molecular-weight protein complexes involving K18/K8, suggesting early-stage Mallory body formation, as observed in chronic liver injury. Mass spectrometry identified cytoskeletal proteins, such as vimentin and periplakin, and regulatory proteins, such as ATP synthase subunit β and PI3K adapter protein, as K18-crosslinked partners. These results suggest that TG1/TG2-mediated aggregation of K18 sequesters essential structural and survival proteins, promoting hepatocyte apoptosis. Targeting these pathological interactions may provide a novel therapeutic strategy to mitigate liver fibrosis and improve hepatocyte survival.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277047","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

Differential regulation of translational stress responses by herpesvirus ubiquitin deconjugases. 疱疹病毒泛素解结剂对翻译应激反应的差异调控。

IF 4.2

The FEBS journal Pub Date : 2025-10-12 DOI: 10.1111/febs.70278

Jiangnan Liu, Noemi Nagy, Carlos Mario Ayala-Torres, Maria G Masucci

{"title":"Differential regulation of translational stress responses by herpesvirus ubiquitin deconjugases.","authors":"Jiangnan Liu, Noemi Nagy, Carlos Mario Ayala-Torres, Maria G Masucci","doi":"10.1111/febs.70278","DOIUrl":"https://doi.org/10.1111/febs.70278","url":null,"abstract":"The strategies adopted by viruses to counteract the potential antiviral effects of ribosomal quality control (RQC) that regulates the fidelity of protein translation, ribosome recycling, and the activation of ribosomal and integrated stress responses are poorly understood. Here, we investigated the capacity of the viral ubiquitin deconjugase (vDUB) encoded in the large tegument protein of human pathogenic herpesviruses to interfere with the triggering of RQC upon the induction of translational stress in cytosolic and endoplasmic reticulum (ER)-associated ribosomes. We found that the vDUBs encoded by Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and Kaposi sarcoma virus (KSHV) share the capacity to counteract the ubiquitination of RPS10, RPS20, and RPS3, and the UFMylation of RPL26 in cells treated with the translation elongation inhibitor anisomycin (ANS), which resulted in the rescue of model RQC and ER-RQC substrates from proteasome- and lysosome-dependent degradation, readthrough of stall-inducing mRNAs, and inhibition of ER-phagy. In contrast, while inhibiting the ubiquitination of RPS10, RPS20, and RPS3, and rescuing RQC substrates almost as efficiently as the homologs, the herpes simplex virus-1 (HSV1) encoded vDUB failed to counteract RPL26 UFMylation. Furthermore, it was unable to rescue the ER-RQC substrate or inhibit ER-phagy, nor did it promote ZAKα phosphorylation or activate the ISR. Our findings pinpoint important differences in the strategies adopted by these human viruses for regulating translational stress responses.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277045","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

Binding of Bacillus subtilis dynamin-like protein DynA to the bacterial membrane is essential for effective phage defense. 枯草芽孢杆菌动力蛋白样蛋白DynA与细菌膜的结合是有效的噬菌体防御所必需的。

IF 4.2

The FEBS journal Pub Date : 2025-10-09 DOI: 10.1111/febs.70282

Samia Shafqat, Urska Repnik, Marc Bramkamp

{"title":"Binding of Bacillus subtilis dynamin-like protein DynA to the bacterial membrane is essential for effective phage defense.","authors":"Samia Shafqat, Urska Repnik, Marc Bramkamp","doi":"10.1111/febs.70282","DOIUrl":"https://doi.org/10.1111/febs.70282","url":null,"abstract":"Bacterial dynamin-like proteins are large GTPases that play crucial roles in membrane dynamics. Bacillus subtilis dynamin-like protein A (DynA), a two-headed bacterial dynamin-like protein, possesses membrane-binding and membrane-tethering functions in trans. The formation of large DynA clusters on bacterial membranes in response to pore-forming antibiotics and phages demonstrates its potential role in maintaining bacterial membrane integrity under various environmental stresses. In this study, we identified the membrane-binding site of B. subtilis DynA within the D1 subunit of the protein that includes positively charged lysine residues K360 and K367, as well as hydrophobic phenylalanine residues F363, F364, and F365. For experimental validation, recombinant proteins with amino acid substitutions in the lysine and phenylalanine residues were produced and used in liposome binding assays. Nonconservative substitutions led to a complete loss of DynA's membrane-binding capability. In vivo data showed strains with DynA variants lacking membrane-binding capability exhibit significantly increased susceptibility to phage infection compared with wild-type cells, further emphasizing the importance of DynA's membrane interaction in conferring phage resistance. Our findings bridge the gap between the structural characteristics of DynA and its functional implications in maintaining bacterial membrane integrity and mediating phage resistance.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260484","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

Exploring the influence of lid region residues on fatty acid selectivity in a lipase originating from Rhizopus oryzae. 探讨米根霉脂肪酶中盖区残基对脂肪酸选择性的影响。

IF 4.2

The FEBS journal Pub Date : 2025-10-09 DOI: 10.1111/febs.70284

Zehui Dong, Majid Haddad Momeni, Kim Olofsson, Eva Nordberg Karlsson

{"title":"Exploring the influence of lid region residues on fatty acid selectivity in a lipase originating from Rhizopus oryzae.","authors":"Zehui Dong, Majid Haddad Momeni, Kim Olofsson, Eva Nordberg Karlsson","doi":"10.1111/febs.70284","DOIUrl":"https://doi.org/10.1111/febs.70284","url":null,"abstract":"Lipases are vital in modifying lipid substrates across industries such as food, cosmetics, and pharmaceuticals. Among their features, fatty acid selectivity is particularly important for industrial applications. Rhizopus oryzae lipase (ROL) stands out for its high selectivity and broad applicability. In this study, we engineered single-residue variants of ROL by targeting Ala89 and Phe95 in its lid region. Additionally, a lid-swap chimera was created by replacing ROL's 15-residue lid with that of the homologous lipase from Rhizomucor miehei (RML). These variants were expressed and characterized to assess changes in substrate selectivity. Our results highlight the lid's key role in determining fatty acid preference. Notably, mutating Phe95 to smaller residues (Ile or Ala) significantly increased selectivity toward medium-chain fatty acid (MCFA) esters. In contrast, substituting Ala89 with bulkier residues (Phe or Trp) reduced activity-except in the lid-swap variant. Interestingly, although the lid-swap variant contains Trp89, the surrounding smaller, non-conserved residues may alleviate steric hindrance. This chimera retained high activity but shifted its preference from MCFAs to long-chain fatty acids (LCFAs), a novel observation. Overall, the engineered variants exhibited distinct substrate preferences without compromising thermostability, suggesting their potential for tailored applications in food, nutrition, and cosmetic industries.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254348","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

Distinct and potent vitamin D hydroxylation activity acquired by the CYP3A4 I301T single amino acid substitution causes type 3 rickets. 通过CYP3A4 I301T单氨基酸取代获得的独特而有效的维生素D羟基化活性导致3型佝偻病。

IF 4.2

The FEBS journal Pub Date : 2025-10-05 DOI: 10.1111/febs.70277

Naoto Nakaya, Ryota Sakamoto, Hiroki Mano, Bunzo Mikami, Hiromasa Imaishi, Kazuo Nagasawa, Toshiyuki Sakaki, Kaori Yasuda

{"title":"Distinct and potent vitamin D hydroxylation activity acquired by the CYP3A4 I301T single amino acid substitution causes type 3 rickets.","authors":"Naoto Nakaya, Ryota Sakamoto, Hiroki Mano, Bunzo Mikami, Hiromasa Imaishi, Kazuo Nagasawa, Toshiyuki Sakaki, Kaori Yasuda","doi":"10.1111/febs.70277","DOIUrl":"https://doi.org/10.1111/febs.70277","url":null,"abstract":"The cytochrome P450 3A4 (CYP3A4) variant I301T has been associated with type 3 rickets, which is characterized by reduced serum calcium and significantly decreased levels of 25-hydroxyvitamin D3 [25(OH)D3] and 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. Although enhanced 4-hydroxylation of these metabolites was previously proposed as the underlying mechanism causing the disease, the precise enzymatic basis remained unclear. In this study, we investigated the enzymatic properties of CYP3A4-I301T using membrane fractions from recombinant Escherichia coli expressing the variant. Surprisingly, we found that CYP3A4-I301T efficiently produced additional metabolites compared to the wild-type CYP3A4, including 11α,25-dihydroxyvitamin D3 and 1α,11α,25-trihydroxyvitamin D3, which have much lower affinity for the vitamin D receptor than do 25(OH)D3 and 1α,25(OH)2D3, respectively. Docking simulations suggested that the 3β-hydroxyl group of 25(OH)D3 forms a hydrogen bond with Thr301 of CYP3A4-I301T, while the 25-hydroxyl group interacts with Arg372 and Glu374, favoring hydroxylation at the 11α-position. These results indicate that the I301T mutation confers a gain-of-function phenotype on CYP3A4, enhancing its ability to metabolize 25(OH)D3 and 1α,25(OH)2D3 into low-activity derivatives. This enzymatic shift likely contributes to substrate depletion and impaired calcium homeostasis in affected individuals. Our findings provide new mechanistic insight into the pathological consequences of a single amino acid substitution in CYP3A4 and expand the understanding of enzyme gain-of-function mutations in metabolic disorders.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234621","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

Structural investigation of human U6 snRNA recognition by spliceosomal recycling factor SART3 RNA recognition motifs. 剪接体再循环因子SART3 RNA识别基序对人U6 snRNA识别的结构研究。

IF 4.2

The FEBS journal Pub Date : 2025-10-05 DOI: 10.1111/febs.70275

Iktae Kim, Kyeong-Mi Bang, So Young An, Changkon Park, Ji-Yeon Shin, Youngim Kim, Hyun Kyu Song, Jeong-Yong Suh, Nak-Kyoon Kim

引用次数: 0

Evolution of lysine and arginine biosynthesis revealed by substrate specificity of lysine biosynthetic enzymes in Thermus thermophilus. 嗜热热菌赖氨酸生物合成酶的底物特异性揭示了赖氨酸和精氨酸生物合成的进化。

IF 4.2

The FEBS journal Pub Date : 2025-10-05 DOI: 10.1111/febs.70274

Wenyuan Shi, Ayako Yoshida, Saori Kosono, Makoto Nishiyama

{"title":"Evolution of lysine and arginine biosynthesis revealed by substrate specificity of lysine biosynthetic enzymes in Thermus thermophilus.","authors":"Wenyuan Shi, Ayako Yoshida, Saori Kosono, Makoto Nishiyama","doi":"10.1111/febs.70274","DOIUrl":"https://doi.org/10.1111/febs.70274","url":null,"abstract":"Metabolic pathways are considered to originate from broad-specificity ancestors that later diverged into specialized routes. Thermus thermophilus possesses an unusual amino group carrier protein (AmCP)-mediated lysine biosynthetic pathway alongside a canonical arginine biosynthetic pathway. Although each route is considered specific to its cognate amino acid, several lysine biosynthetic enzymes have been shown to accept arginine intermediates. We herein investigated [LysW]-aminoadipate kinase (LysZ; EC:2.7.2.17) and [LysW]-L-2-aminoadipate 6-phosphate reductase (LysY; EC:1.2.1.103), which catalyze the second and third steps, respectively, in the conversion of α-aminoadipate (AAA) to lysine using amino group carrier protein LysW (AmCP), to define their specificity and evolutionary origin. To examine the potential promiscuity, we engineered LysX variants capable of synthesizing LysW-Glu, an artificial LysW-bound analogue that mimics an arginine pathway intermediate. LysZ exhibited activity for LysW-Glu that was approximately 60% of the original activity for LysW-AAA. The activity of LysY for LysW-Glu phosphate was estimated to be approximately 15-20% of that observed with LysW-AAA phosphate. The present study revealed that both enzymes can also act on an arginine biosynthetic intermediate, but with distinct degrees of efficiency. Phylogenetic reconstructions further suggested that an AmCP-mediated biosynthetic pathway represents a primitive route for the synthesis of lysine and arginine in a primordial cell. More generally, the results obtained herein will contribute to a more detailed understanding of the evolutionary strategies employed by nature to specialize and expand metabolic pathways and adjust enzyme promiscuity.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234623","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

Heterologous plastoquinone production using a newly identified O₂-dependent cyanobacterial hydroxylase. 利用一种新发现的o2依赖性蓝藻羟化酶生产异源质体醌。

IF 4.2

The FEBS journal Pub Date : 2025-10-02 DOI: 10.1111/febs.70272

Morgane Roger-Margueritat, Margot Beltran, Juliette Schnoebelen, Laura Flandrin, Wafa Rezali, Eline Michel, Sophie S Abby, Fabien Pierrel

{"title":"Heterologous plastoquinone production using a newly identified O2-dependent cyanobacterial hydroxylase.","authors":"Morgane Roger-Margueritat, Margot Beltran, Juliette Schnoebelen, Laura Flandrin, Wafa Rezali, Eline Michel, Sophie S Abby, Fabien Pierrel","doi":"10.1111/febs.70272","DOIUrl":"https://doi.org/10.1111/febs.70272","url":null,"abstract":"Isoprenoid quinones constitute a class of redox lipids that are indispensable for electron transfer in a variety of cellular functions. For instance, plastoquinone, an integral component of plants, algae and Cyanobacteriota, plays a pivotal role in photosynthesis. Isoprenoid quinones are biosynthesised via evolutionary-related pathways, in which some steps are still incompletely characterised. In this study, we confirm the identity of the PlqH enzyme, a flavin-dependent monooxygenase (FMO) conserved in photosynthetic cyanobacteria, which possesses a regioselective hydroxylase activity required for plastoquinone biosynthesis. Phylogenetic analyses demonstrate that cyanobacterial PlqH homologues originated from FMOs involved in bacterial ubiquinone biosynthesis. The synthesis of plastoquinone by Escherichia coli was achieved by expressing two heterologous genes in a genetically engineered strain, which was optimised to produce plastoquinone levels comparable to those of natural ubiquinone. However, plastoquinone was unable to replace ubiquinone in several cellular processes in E. coli, suggesting that fine structural and thermodynamic constraints both play a significant role in the function of quinones.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215127","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

Phylogenetic reconciliation provides new insights into the evolutionary diversification of the glutamine synthetase gene family in seed plants. 系统发育和解为种子植物谷氨酰胺合成酶基因家族的进化多样化提供了新的见解。

IF 4.2

The FEBS journal Pub Date : 2025-09-29 DOI: 10.1111/febs.70276

Elena Aledo, Rafael Antonio Cañas, Francisco R Cantón, Juan Carlos Aledo

{"title":"Phylogenetic reconciliation provides new insights into the evolutionary diversification of the glutamine synthetase gene family in seed plants.","authors":"Elena Aledo, Rafael Antonio Cañas, Francisco R Cantón, Juan Carlos Aledo","doi":"10.1111/febs.70276","DOIUrl":"https://doi.org/10.1111/febs.70276","url":null,"abstract":"Glutamine synthetase (GS) catalyzes the incorporation of ammonium into glutamate, a crucial reaction in nitrogen metabolism. Despite advances in plant genomics, the evolutionary relationships among GS isoforms in seed plants remain incompletely understood. In this study, we selected 155 GS genes from 45 phylogenetically well-characterized seed plant species. Our analyses consistently support the existence of three distinct evolutionary lineages of GS genes in seed plants: GS2 (chloroplastic), and GS1a and GS1b (cytosolic). Using a Bayesian molecular clock dating approach, we estimate that GS2 diverged approximately 560 million years ago, whereas GS1a and GS1b began to diverge around 70 million years later. Additionally, we developed orthgs, a software tool that implements tree reconciliation and enables analyses of orthology and paralogy among GS enzymes. Phylogenetic reconciliation offers new insights into the evolutionary dynamics of the GS gene family in plants, revealing the existence of new paralogs of GS1a and GS2. Most of the genomes analyzed contain multiple paralogs of GS1b, whereas GS1a and GS2 appear as singleton genes. Although these single-copy genes have traditionally been considered orthologs, we present evidence challenging this assumption. Thus, our findings suggest that both GS1a and GS2 have undergone multiple duplication events throughout evolutionary history, similar to GS1b. However, unlike GS1b, only a single paralog of GS1a (or GS2) is retained per genome. Overall, our study reshapes the understanding of GS gene family evolution in seed plants by uncovering hidden duplication events in GS1a and GS2, highlighting dynamic evolutionary patterns previously overlooked in this gene family.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194265","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

A short peptide derived from late embryogenesis abundant proteins enhances acid tolerance in Escherichia coli via modulation of two-component regulatory systems. 来自胚胎发育晚期丰富蛋白的短肽通过调节双组分调控系统增强大肠杆菌的耐酸能力。

IF 4.2

The FEBS journal Pub Date : 2025-09-27 DOI: 10.1111/febs.70268

Khaled Metwally, Shinya Ikeno

{"title":"A short peptide derived from late embryogenesis abundant proteins enhances acid tolerance in Escherichia coli via modulation of two-component regulatory systems.","authors":"Khaled Metwally, Shinya Ikeno","doi":"10.1111/febs.70268","DOIUrl":"https://doi.org/10.1111/febs.70268","url":null,"abstract":"Late embryogenesis abundant (LEA) proteins are responsible for facilitating tolerance to various environmental stresses across diverse organisms. Group 3 LEA proteins are characterised by the presence of 11-mer amino acid motifs, which inspired the design of short peptides with similar protective functions. Here, we designed a LEA peptide variant (LEA-K) and evaluated its acid tolerance capacity in Escherichia coli BL21 (DE3) at pH4. Expression of LEA-K peptide improved the bacterial viability under acidic stress, suggesting its protective functions. To explore the molecular mechanism of such tolerance, we combined the RNA-sequencing (RNA-Seq) technique and molecular docking simulations. Transcriptome analysis identified 283 differentially expressed genes (DEGs), and revealed metabolic reprogramming and activation of stress-related pathways, including proton pumping, biofilm formation, and stress responsive systems. Functional enrichment analysis suggested a key role of two-component regulatory systems (TCSs) such as reactive chlorine species (RCS), sensor histidine kinase BtsS/transcriptional regulatory protein BtsR, and DNA-binding dual transcriptional regulator OmpR/sensor histidine kinase EnvZ. Protein-peptide docking simulations indicated potential interactions between LEA-K and these TCSs, suggesting a mechanistic basis of the observed transcriptional modulation. These findings propose previously unknown functional roles for LEA peptides, not only acting as molecular shields but also as signal-transducing modulators. This work expands our understanding of stress tolerance mechanisms and presents a new avenue for engineering stress-resilient bacterial systems.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180799","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