Frontiers in Molecular Biosciences最新文献

{"title":"Recent advances of lysine lactylation in prokaryotes and eukaryotes.","authors":"Wenjuan Zhao, Jiayi Xin, Xin Yu, Zhifang Li, Nan Li","doi":"10.3389/fmolb.2024.1510975","DOIUrl":"10.3389/fmolb.2024.1510975","url":null,"abstract":"<p><p>Lysine lactylation is a newly discovered protein post-translational modification that plays regulatory roles in cell metabolism, growth, reprogramming, and tumor progression. It utilizes lactate as the modification precursor, which is an end product of glycolysis while functioning as a signaling molecule in cells. Unlike previous reviews focused primarily on eukaryotes, this review aims to provide a comprehensive summary of recent knowledge about lysine lactylation in prokaryotes and eukaryotes. The current identification and enrichment strategies for lysine lactylation are introduced, and the known readers, writers, and erasers of this modification are summarized. In addition, the physiological and pathological implications of lysine lactylation are reviewed for different organisms, especially in prokaryotic cells. Finally, we end with a discussion of the limitations of the studies so far and propose future directions for lysine lactylation investigations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1510975"},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the biophysical mechanisms of oleate hydratase association with membranes.","authors":"William A Lathram, Robert J Neff, Ashley N Zalla, James D Brien, Vivekanandan Subramanian, Christopher D Radka","doi":"10.3389/fmolb.2024.1504373","DOIUrl":"10.3389/fmolb.2024.1504373","url":null,"abstract":"<p><p>This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from <i>Staphylococcus aureus</i>, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to phosphatidylglycerol unilamellar vesicles. Our results reveal that OhyA preferentially binds to vesicles with moderate curvature, while the presence of substrate fatty acids slightly enhanced the overall interaction despite reducing the binding affinity by 3- to 4-fold. Complementary phosphorus-31 (³¹P) NMR spectroscopy further demonstrated two distinct binding modes: a fast-exchange interaction at lower protein concentrations and a longer lasting interaction at higher protein concentrations, likely reflecting cooperative oligomerization. These findings highlight the reversible, non-stoichiometric nature of OhyA•membrane interactions, with dynamic binding behaviors influenced by protein concentration and lipid environment. This research provides new insights into the dynamic behavior of OhyA on bacterial membranes, highlighting that initial interactions are driven by lipid-mediated protein binding, while sustained interactions are primarily governed by the protein:lipid molar ratio rather than the formation of new, specific lipid-protein interactions. These findings advance our understanding of the biophysical principles underlying OhyA's role in bacterial membrane function and virulence.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504373"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial molecular motors in biological applications.","authors":"Fuli Fan, Songshen Liu, Yuting Yan, Peng Zhang, Kui Che","doi":"10.3389/fmolb.2024.1510619","DOIUrl":"10.3389/fmolb.2024.1510619","url":null,"abstract":"<p><p>Molecular motors are the cornerstone for the maintenance of living systems and mediate almost all fundamental processes involved in cellular trafficking. The intricate mechanisms underlying natural molecular motors have been elucidated in detail, inspiring researchers in various fields to construct artificial systems with multi-domain applications. This review summarises the characteristics of molecular motors, biomimetic approaches for their design and operation, and recent biological applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1510619"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors.","authors":"Jingtao Wang, Qidong Zhang, Wu Fan, Qingzhao Shi, Jian Mao, Jianping Xie, Guobi Chai, Chenglei Zhang","doi":"10.3389/fmolb.2024.1498796","DOIUrl":"10.3389/fmolb.2024.1498796","url":null,"abstract":"<p><p>Olfactory receptors, classified as G-protein coupled receptors (GPCRs), have been a subject of scientific inquiry since the early 1950s. Historically, investigations into the sensory mechanisms of olfactory receptors were often confined to behavioral characteristics in model organisms or the expression of related proteins and genes. However, with the development of cryo-electron microscopy techniques, it has gradually become possible to decipher the specific structures of olfactory receptors in insects and humans. This has provided new insights into the binding mechanisms between odor molecules and olfactory receptors. Furthermore, due to the rapid advancements in related fields such as computer simulations, the prediction and exploration of odor molecule binding to olfactory receptors have been progressively achieved through molecular dynamics simulations. Through this comprehensive review, we aim to provide a thorough analysis of research related to the binding mechanisms between odor molecules and olfactory receptors from the perspectives of structural biology and molecular dynamics simulations. Finally, we will provide an outlook on the future of research in the field of olfactory receptor sensory mechanisms.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1498796"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 N17 domain of huntingtin as a multifaceted player in Huntington's disease.","authors":"Hyunju Cho","doi":"10.3389/fmolb.2024.1527313","DOIUrl":"10.3389/fmolb.2024.1527313","url":null,"abstract":"<p><p>Huntington's disease (HD) is primarily caused by the aberrant aggregation of the N-terminal exon 1 fragment of mutant huntingtin protein (mHttex1) with expanded polyglutamine (polyQ) repeats in neurons. The first 17 amino acids of the N-terminus of Httex1 (N17 domain) immediately preceding the polyQ repeat domain are evolutionarily conserved across vertebrates and play multifaceted roles in the pathogenesis of HD. Due to its amphipathic helical properties, the N17 domain, both alone and when membrane-associated, promotes mHttEx1 aggregation. Diverse post-translational modifications (PTMs) in the N17 domain alter the aggregation state, thus modulating the cellular toxicity of mHttex1. Furthermore, the N17 domain serves as a nuclear export signal (NES) and mediates the cytoplasmic localization of mHttex1. This review summarizes the four main roles of the N17 domain in regulating HD pathology and discusses potential therapeutic approaches targeting this N17 domain to mitigate HD progression.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1527313"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticarcinogenic cationic peptides derived from tryptic hydrolysis of β-lactoglobulin.","authors":"Eman Ibrahem, Ali Osman, Hefnawy Taha, Mohamed F Abo El-Maati, Basel Sitohy, Mahmoud Sitohy","doi":"10.3389/fmolb.2024.1444457","DOIUrl":"10.3389/fmolb.2024.1444457","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the tryptic hydrolysis of β-lactoglobulin (BLG) for 30, 60, 90, and 120 min at 1/200 E/S (enzyme/substrate ratio, w/w) to prepare potentially anticarcinogenic peptides.</p><p><strong>Methods: </strong>The properties of hydrolysates were characterized, including degree of hydrolysis, free amino acids, SDS-PAGE, FTIR, and antioxidant activity employing DPPH-assay, β-carotene/linoleic acid, and FRAP assay.</p><p><strong>Results: </strong>BLG tryptic hydrolysate produced after 60 min hydrolysis recorded the highest antioxidant activity, and LCMS analysis revealed 162 peptides of molecular masses ranging from 800 to 5671Da, most of them are of hydrophobic nature. Within the low-MW peptide group (24 peptides), there were nine hydrophobic basic (HB) and seven hydrophobic acidic (HA), representing 38% and 29%, respectively. The HB peptides may be responsible for the considerable biological activity of the hydrolysate. With dominant basic character supporting the carcinogenic activity of this hydrolysate. The <i>in vitro</i> anticancer activity against Mcf-7, Caco-2, and A-549 human cancer cell lines proliferation by MTT assay recorded IC_50% at 42.8, 76.92, and 45.93 μg/mL, respectively. Treating each cell line with IC_50% of the hydrolysate for 24 h increased the apoptosis by enhancing the expression of caspase-9 by 5.66, 7.97, and 3.28 folds over the untreated control and inhibited angiogenesis by reducing VEGFR-2 expression by about 56, 76, and 70%, respectively, indicating strong anticancer and antiangiogenic actions on human cancer cells. BLG tryptic hydrolysate may serve as a natural anticarcinogenic agent. The results of this study demonstrated that BLG hydrolysates have direct anticancer and antiangiogenic effects on human cancer cells. The chemical composition and characteristics of the BLG tryptic hydrolysate influence these biological and anticancer activities. The tryptic hydrolysates were generally effective against the three cancer cell lines studied (Mcf-7, Caco-2, and A-549). This effectiveness was assessed by measuring cell proliferation using the MTT assay and by evaluating their impact on angiogenesis through inhibition of VEGFR-2 activity.</p><p><strong>Discussion: </strong>Future studies may focus on enhancing the anticarcinogenic effectiveness of the peptides by isolating and evaluating the most prominent individual peptide and varying the treatment conditions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1444457"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of cancer cell volatile organic compounds: their metabolism and evolution.","authors":"Takeshi Furuhashi, Kanako Toda, Wolfram Weckwerth","doi":"10.3389/fmolb.2024.1499104","DOIUrl":"10.3389/fmolb.2024.1499104","url":null,"abstract":"<p><p>Cancer is ranked as the top cause of premature mortality. Volatile organic compounds (VOCs) are produced from catalytic peroxidation by reactive oxygen species (ROS) and have become a highly attractive non-invasive cancer screening approach. For future clinical applications, however, the correlation between cancer hallmarks and cancer-specific VOCs requires further study. This review discusses and compares cellular metabolism, signal transduction as well as mitochondrial metabolite translocation in view of cancer evolution and the basic biology of VOCs production. Certain cancerous characteristics as well as the origin of the ROS removal system date back to procaryotes and early eukaryotes and share commonalities with non-cancerous proliferative cells. This calls for future studies on metabolic cross talks and regulation of the VOCs production pathway.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1499104"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin reshapes bone metabolic homeostasis to delay age-related osteoporosis by regulating the multipotent differentiation of BMSCs via Wnt pathway.","authors":"Shangman Xing, Yifan Ma, Bing Song, Min Bai, Kexin Wang, Wenjing Song, Tingting Cao, Chao Guo, Yanying Zhang, Zhandong Wang, Yongfeng Wang","doi":"10.3389/fmolb.2024.1524978","DOIUrl":"10.3389/fmolb.2024.1524978","url":null,"abstract":"<p><strong>Introduction: </strong>Bone aging is linked to changes in the lineage differentiation of bone marrow stem cells (BMSCs), which show a heightened tendency to differentiate into adipocytes instead of osteoblasts. The therapeutic potential of irisin in addressing age-related diseases has garnered significant attention. More significantly, irisin has the capacity to enhance bone mass recovery and sustain overall bone health. Its mechanism of action in preventing osteoporosis has generated considerable interest within the research community. Nonetheless, the targeting effect of irisin on age-related osteoporosis and its underlying molecular biological mechanisms remain unclear.</p><p><strong>Methods: </strong>The specific role of irisin in osteogenic-adipogenic differentiation in young or aging BMSCs was evaluated by multiple cells staining and quantitative real-time PCR (RT-qPCR) analysis. RNA-seq and protein Western blotting excavated and validated the key pathway by which irisin influences the fate determination of aging BMSCs. The macroscopic and microscopic changes of bone tissue in aging mice were examined using Micro-computed tomography (Micro-CT) and morphological staining.</p><p><strong>Results: </strong>It was noted that irisin affected the multilineage differentiation of BMSCs in a manner dependent on the dosage. Simultaneously, the Wnt signaling pathway might be a crucial mechanism through which irisin sustains the bone-fat balance in aging BMSCs and mitigates the decline in pluripotency. <i>In vivo</i>, irisin reduced bone marrow fat deposition in aging mice and effectively alleviating the occurrence of bone loss.</p><p><strong>Conclusion: </strong>Irisin mediates the Wnt signaling pathway, thereby influencing the fate determination of BMSCs. In addition, it is essential for preserving metabolic equilibrium in the bone marrow microenvironment and significantly contributes to overall bone health. The findings provide new evidence for the use of iris extract in the treatment of age-related osteoporosis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1524978"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the shared gene signatures and mechanism among three autoimmune diseases by bulk RNA sequencing integrated with single-cell RNA sequencing analysis.","authors":"Xiaofang Liu, Bin Li, Yuxi Lin, Xueying Ma, Yingying Liu, Lili Ma, Xiaomeng Ma, Xia Wang, Nanjing Li, Xiaoyun Liu, Xiaohong Chen","doi":"10.3389/fmolb.2024.1520050","DOIUrl":"10.3389/fmolb.2024.1520050","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence underscores the comorbidity mechanisms among autoimmune diseases (AIDs), with innovative technologies such as single-cell RNA sequencing (scRNA-seq) significantly advancing the explorations in this field. This study aimed to investigate the shared genes among three AIDs-Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA) using bioinformatics databases, and to identify potential biomarkers for early diagnosis.</p><p><strong>Methods: </strong>We retrieved transcriptomic data of MS, SLE, and RA patients from public databases. Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify disease-associated modules. Functional enrichment analyses and Protein-Protein Interaction (PPI) network was constructed. We used machine learning algorithms to select candidate biomarkers and evaluate their diagnostic value. The Cibersort algorithm was and scRNA-seq analysis was performed to identify key gene expression patterns and assess the infiltration of immune cells in MS patients. Finally, the biomarkers' expression was validated in human and mice experiments.</p><p><strong>Results: </strong>Several shared genes among MS, SLE, and RA were identified, which play crucial roles in immune responses and inflammation regulation. PPI network analysis highlighted key hub genes, some of which were selected as candidate biomarkers through machine learning algorithms. Receiver Operating Characteristic (ROC) curve analysis indicated that some genes had high diagnostic value (Area Under the Curve, AUC >0.7). Immune cell infiltration pattern analysis showed significant differences in the expression of various immune cells in MS patients. scRNA-seq analysis revealed clusters of genes that were significantly upregulated in the single cells of cerebrospinal fluid in MS patients. The expression of shared genes was validated in the EAE mose model. Validation using clinical samples confirmed the expression of potential diagnostic biomarkers.</p><p><strong>Conclusion: </strong>This study identified shared genes among MS, SLE, and RA and proposed potential early diagnostic biomarkers. These genes are pivotal in regulating immune responses, providing new targets and theoretical basis for the early diagnosis and treatment of autoimmune diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1520050"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Modelling esophageal adenocarcinoma.","authors":"Hisham F Bahmad, Farah Ballout","doi":"10.3389/fmolb.2024.1550595","DOIUrl":"10.3389/fmolb.2024.1550595","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1550595"},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}