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Cellular signalling of melatonin and its role in metabolic disorders.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-04 DOI: 10.1007/s11033-025-10306-8
Snehasis Tripathy, Subrat Kumar Bhattamisra
{"title":"Cellular signalling of melatonin and its role in metabolic disorders.","authors":"Snehasis Tripathy, Subrat Kumar Bhattamisra","doi":"10.1007/s11033-025-10306-8","DOIUrl":"https://doi.org/10.1007/s11033-025-10306-8","url":null,"abstract":"<p><p>Melatonin released from the pineal gland plays an important role in maintaining the light/dark cycle. Melatonin exerts its effects on various organs through receptor and nonreceptor pathways. Recently, the role of melatonin in various metabolic disorders has been investigated. This review focuses on the molecular pathways associated with melatonin and its role in metabolic disorders. In humans, melatonin acts through two G protein-coupled receptors (MT1 and MT2). Melatonin modulates insulin release, such as elevated insulin levels in the evening compared to morning hours, exerts cardioprotective effects through the cGMP pathway and nitric oxide production in endothelial cells, and controls oxidative stress and apoptosis in myocardial tissue. Melatonin through MT2 receptors increases lipolysis and thermogenesis, which have a positive effect on weight reduction in obese individuals. Currently, most drugs that target melatonin receptors are primarily used to treat neurological disorders. A detailed investigation to explore the role of melatonin and its signalling pathway in peripheral organs is essential to develop therapeutic molecules for managing metabolic disorders.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"193"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative effects of arsenic trioxide and chemotherapy on Chk1 and CDC25 gene expression in gastric cancer cells AGS and MKN45: a potential therapeutic strategy.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-04 DOI: 10.1007/s11033-025-10313-9
Shadi Babaei, Mohsen Nikbakht, Ahmad Majd, Seyed Asadoullah Mousavi
{"title":"Comparative effects of arsenic trioxide and chemotherapy on Chk1 and CDC25 gene expression in gastric cancer cells AGS and MKN45: a potential therapeutic strategy.","authors":"Shadi Babaei, Mohsen Nikbakht, Ahmad Majd, Seyed Asadoullah Mousavi","doi":"10.1007/s11033-025-10313-9","DOIUrl":"https://doi.org/10.1007/s11033-025-10313-9","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a significant global health burden, particularly in East Asia, where it is a leading cause of cancer-related morbidity and mortality. Despite advancements in chemotherapy, the development of chemoresistance continues to undermine the efficacy of standard treatments such as Docetaxel and Oxaliplatin. Arsenic trioxide (ATO) has emerged as a potential therapeutic agent capable of overcoming resistance by targeting DNA repair mechanisms, particularly through the downregulation of Checkpoint Kinase 1 (Chk1). This study investigates the cytotoxic effects of ATO and its capacity to enhance chemotherapy efficacy in GC cells.</p><p><strong>Methods: </strong>AGS and MKN-45 gastric cancer cell lines were exposed to ATO, Docetaxel, Oxaliplatin, and their combinations. Cell viability was assessed via the MTT assay, while Chk1 and CDC25 expressions at the mRNA and protein levels was analyzed using real-time PCR and Western blotting. Statistical analyses were performed using ANOVA and Tukey's post hoc test.</p><p><strong>Results: </strong>The MTT assay revealed significant dose- and time-dependent reductions in cell viability, with combination treatments achieving the most pronounced effects. The greatest cytotoxicity was observed with 4 µM ATO combined with 2500 µM Docetaxel or 100 µM Oxaliplatin, showing a high level of statistical significance (p < 0.0001). Additionally, ATO monotherapy significantly downregulated Chk1 and CDC25 expressions (p < 0.05), while its combination with chemotherapeutic agents further enhanced Chk1 and CDC25 suppressions, with ATO-Docetaxel demonstrating the most pronounced effect (p < 0.01).</p><p><strong>Conclusions: </strong>These findings highlight ATO's potential to sensitize GC cells to chemotherapy by impairing DNA repair mechanisms and inducing synergistic cytotoxicity. ATO holds promise as an adjuvant therapeutic agent for overcoming chemoresistance in gastric cancer.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"198"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of hepatitis B virus surface antigen, IgM and IgG antibodies to hepatitis B virus core antigen in the clinical classification and epidemiological surveillance of HBV infection. 在乙型肝炎病毒感染的临床分类和流行病学监测中检测乙型肝炎病毒表面抗原、乙型肝炎病毒核心抗原的 IgM 和 IgG 抗体。
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-04 DOI: 10.1007/s11033-025-10278-9
Robério Amorim de Almeida Pondé
{"title":"Detection of hepatitis B virus surface antigen, IgM and IgG antibodies to hepatitis B virus core antigen in the clinical classification and epidemiological surveillance of HBV infection.","authors":"Robério Amorim de Almeida Pondé","doi":"10.1007/s11033-025-10278-9","DOIUrl":"https://doi.org/10.1007/s11033-025-10278-9","url":null,"abstract":"<p><p>Hepatitis B virus surface antigen (HBsAg), IgM and IgG antibodies to hepatitis B virus core antigen (anti-HBcIgM and anti-HBcIgG) comprise serological markers of hepatitis B virus (HBV) infection of great importance in the epidemiological surveillance of hepatitis B, since they have been routinely considered for classifying the acute and chronic clinical forms of HBV infection. This classification is established according to the expression and dynamics of these markers in the infected person's bloodstream, which serves as the basis for the differential diagnosis between the two clinical entities. However, in certain circumstances, both acute and chronic infection, the detection of these markers may not occur in the bloodstream, favoring the occurrence of atypical serological profiles of infection, and compromising the correct infection clinical classification. In addition, the complex and varied nature of hepatitis B serological profiles may compromise the health professional's ability to analyze the case and, thus, correctly classify the infection's clinical form. Since the expression of these markers in the bloodstream occurs dynamically, with consequent changes in the patient's serological profile as he progresses towards recovery or chronicity, the diagnosis of acute or chronic infection may also be compromised, if it is established based on the collection of a single sample and without knowing the patient's clinical history and their epidemiological antecedents. This manuscript addresses the sensitivity and specificity of HBsAg, anti-HBcIgM, and anti-HBcIgG serological markers detection in the clinical classification of HBV infection and in the epidemiological surveillance of hepatitis B. This review is covering the clinical and epidemiological interpretations of the markers in and of themselves, not in reference to any specific assays.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"195"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zerumbone-mediated post-ischemic neuroprotection: Reduction of ferroptosis through TFR1 downregulation in vitro.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-04 DOI: 10.1007/s11033-025-10301-z
Gokul S, Fayaz S M, Rajanikant G K
{"title":"Zerumbone-mediated post-ischemic neuroprotection: Reduction of ferroptosis through TFR1 downregulation in vitro.","authors":"Gokul S, Fayaz S M, Rajanikant G K","doi":"10.1007/s11033-025-10301-z","DOIUrl":"https://doi.org/10.1007/s11033-025-10301-z","url":null,"abstract":"<p><p>Emerging studies have identified ferroptosis as a promising therapeutic target, the inhibition of which is hypothesized to mitigate brain injury and subsequent neuronal death following stroke. Zerumbone, a phytochemical sesquiterpene isolated from Zingiber zerumbet Smith, exhibit diverse therapeutic properties across a range of neurological disorders. This study aimed to elucidate the postischemic neuroprotective effects and regulatory impact of zerumbone on ferroptosis-mediated cell death following oxygen‒glucose deprivation/reperfusion (OGD/R) injury. We employed an in vitro OGD/R SH-SY5Y cell model of stroke to evaluate the postischemic neuroprotective effects of zerumbone, a lead molecule identified through literature studies. Moreover, assays were performed to assess how zerumbone affects lipid peroxide levels, intracellular reactive oxygen species (ROS), and mitochondrial membrane integrity. Furthermore, molecular docking simulations were carried out to determine the targets, and western blotting was performed to examine TFR1 protein expression. Zerumbone (0.5 µM) treatment at 1-hour postischemia increased cell viability (72.11 ± 0.98) and mitigated OGD/R-induced ischemic injury. Zerumbone significantly decreased intracellular ROS levels and lipid peroxide production while increasing mitochondrial membrane integrity, suggesting that zerumbone ameliorated OGD/R-induced ischemic injury by inhibiting ferroptosis in vitro. This finding was corroborated by our western blot analysis, which revealed that the antiferroptotic role of zerumbone was distinctly mediated through the downregulation of transferrin receptor 1 (TFR1) protein expression. This communication, for the first time, highlights the feasibility of zerumbone as a promising adjunctive neuroprotective agent against ferroptosis cell death in the context of cerebral stroke. This study lays the groundwork for subsequent in-depth investigations to fully elucidate its therapeutic potential in ischemic stroke treatment.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"201"},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intrinsic and extrinsic modulators of human dental pulp stem cells: advancing strategies for tissue engineering applications.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-025-10281-0
Fatemeh Kavakebian, Alireza Rezapour, Reihaneh Seyedebrahimi, Mohsen Eslami Farsani, Massoumeh Jabbari Fakhr, Saeedeh Zare Jalise, Shima Ababzadeh
{"title":"Intrinsic and extrinsic modulators of human dental pulp stem cells: advancing strategies for tissue engineering applications.","authors":"Fatemeh Kavakebian, Alireza Rezapour, Reihaneh Seyedebrahimi, Mohsen Eslami Farsani, Massoumeh Jabbari Fakhr, Saeedeh Zare Jalise, Shima Ababzadeh","doi":"10.1007/s11033-025-10281-0","DOIUrl":"10.1007/s11033-025-10281-0","url":null,"abstract":"<p><p>This review focuses on dental pulp stem cells (DPSCs) which are mesenchymal stem cells (MSCs) and originating from the neural crest. These cells possess a high capacity for self-renewal and multilineage differentiation. Because of these traits, they represent promising sources for tissue engineering, regenerative medicine, and clinical applications. The objective of this study was to assess the extrinsic and intrinsic factors influencing DPSC characteristics and their potential in tissue engineering. This review discusses the external and internal factors affecting DPSC properties, including proliferation, migration, differentiation, and gene expression post extraction. Additionally, it explores the impact of the microenvironment-its composition and physical properties-and genetic and epigenetic regulation on DPSC behavior. Variations in the microenvironment and genetic regulation play pivotal roles in modulating DPSC functions, including their proliferation and differentiation potential. Intrinsic and extrinsic factors are key barriers to realizing the full therapeutic potential of DPSCs. A deeper understanding of the extrinsic and intrinsic factors affecting DPSC behavior is critical for optimizing their use in regenerative medicine, particularly for dental and craniofacial applications. Although DPSCs hold significant promise, challenges remain, and this review provides insights into the current limitations and future directions for DPSC-based therapies. Researchers and clinicians are offered a comprehensive resource for advancing the field.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"190"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The paradoxical role of SERPINB5 in gastrointestinal cancers: oncogene or tumor suppressor?
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-025-10293-w
Shuyan Zeng, Jiayu Zhang, Wanyi Jiang, Chunyan Zeng
{"title":"The paradoxical role of SERPINB5 in gastrointestinal cancers: oncogene or tumor suppressor?","authors":"Shuyan Zeng, Jiayu Zhang, Wanyi Jiang, Chunyan Zeng","doi":"10.1007/s11033-025-10293-w","DOIUrl":"https://doi.org/10.1007/s11033-025-10293-w","url":null,"abstract":"<p><strong>Background: </strong>SERPINB5, also known as Maspin, is a non-inhibitory member of the serine protease inhibitor superfamily. SERPINB5 exerts diverse effects on a variety of human cancers, including cell proliferation, angiogenesis, apoptosis, tumor invasion, and metastasis. SERPINB5 has traditionally been regarded as a tumor suppressor gene, but emerging evidences supports its oncogenic properties.</p><p><strong>Methods: </strong>We conducted a comprehensive review of the existing literature on SERPINB5 in gastrointestinal cancers, synthesizing data on its expression patterns, subcellular localization, epigenetic modifications, and clinical significance.</p><p><strong>Results: </strong>Depending on its subcellular localization and epigenetic modifications, SERPINB5 demonstrate either protumor or antitumor activity in different gastrointestinal cancers, such as colorectal cancer, gastric cancer, pancreatic cancer, gallbladder cancer and liver cancer. We elucidate its potential as a predictive and prognostic biomarker, with a focus on its implications for diagnosis, prognosis, and therapeutic intervention, emphasizing its utility in early lesion detection and treatment.</p><p><strong>Conclusions: </strong>SERPINB5 plays a complex and context-dependent role in gastrointestinal cancers, highlighting further research to dissect the true significance of SERPINB5 expression and the molecular mechanisms underlying its divergent clinical behaviors in cancer.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"188"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome-wide identification and comprehensive analysis of the FtsH gene family in wheat.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-025-10243-6
Yuwei Li, Hao Liu, Xiaoyu Wang, Bo Wang
{"title":"Genome-wide identification and comprehensive analysis of the FtsH gene family in wheat.","authors":"Yuwei Li, Hao Liu, Xiaoyu Wang, Bo Wang","doi":"10.1007/s11033-025-10243-6","DOIUrl":"https://doi.org/10.1007/s11033-025-10243-6","url":null,"abstract":"<p><strong>Background: </strong>The filamentation temperature-sensitive H (FtsH) gene family, which is known to play a critical role in plant growth and development by regulating photosynthesis, chloroplast development, and response to plant stress, has been extensively studied in various species. However, the FtsH gene family in wheat has not been previously documented.</p><p><strong>Methods and results: </strong>In this study, 38 TaFtsH gene family members were identified, divided into eight groups and unevenly distributed across various chromosomes. Analysis of gene structure and conserved motifs revealed that TaFtsH genes within the same taxon share similar gene structures and conserved motifs. Further collinearity analysis provided insights into the evolutionary history of TaFtsH genes. Examination of cis-acting elements in the promoter region of TaFtsH genes revealed the presence of developmental and stress response elements in genes. The expression pattern of the wheat FtsH gene under various abiotic stresses was analyzed using real-time fluorescence quantitative PCR. Additionally, transient expression in tobacco verified the localization of the TaFtsH11-B protein in chloroplasts.</p><p><strong>Conclusions: </strong>These findings collectively contribute to laying the groundwork for the functional characterization of TaFtsH genes.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"186"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell RNA sequencing of neonatal cortical astrocytes reveals versatile cell clusters during astrocyte-neuron conversion.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-025-10309-5
Jiaxue Cha, Peng Zeng, Hui Zong, Jiayi Zhao, Jiayao Chen, Haowei Zuo, Bowen Zhang, Changjie Shi, Jing Li, Qiuhong Hua, Zixin Wang, Yujun Hou, Ru Zhang
{"title":"Single-cell RNA sequencing of neonatal cortical astrocytes reveals versatile cell clusters during astrocyte-neuron conversion.","authors":"Jiaxue Cha, Peng Zeng, Hui Zong, Jiayi Zhao, Jiayao Chen, Haowei Zuo, Bowen Zhang, Changjie Shi, Jing Li, Qiuhong Hua, Zixin Wang, Yujun Hou, Ru Zhang","doi":"10.1007/s11033-025-10309-5","DOIUrl":"10.1007/s11033-025-10309-5","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes are extensively utilized as starting cells for neuronal conversion. Our previous study discovered that a portion of primary cultured mouse neonatal cortical astrocytes can be directly converted into neurons after exposure to a neurogenic induction condition. Recent in vivo studies have demonstrated astrocyte heterogeneity in terms of their developmental origin, molecular profile, physiology, and functional outputs. We hypothesized that the heterogeneity of primary astrocytes in our study could influence their conversion potential.</p><p><strong>Methods and results: </strong>We performed single-cell RNA sequencing on cells harvested at key time points during in vitro astrocyte-to-neuron conversion, specifically on Day 1 and Day 9. Through single-cell RNA sequencing analysis, we identified several subpopulations of astrocytes, labeled as Astrocyte 1 to Astrocyte 3, based on distinct gene expression patterns. Pseudotime trajectory analysis predicted the existence of three distinct cell states throughout the conversion process. Astrocyte 3 exhibited a higher propensity for neuronal conversion, with proliferation genes like Mki67 being highly expressed. Additionally, several candidate genes were identified as potentially crucial in the conversion process. Astrocyte 3 is considered a unique subtype population of astrocytes.</p><p><strong>Conclusions: </strong>Our investigation underscores the diversity of primary neonatal cortical astrocytes and provides critical insights into the potential for astrocyte-to-neuron conversion, which may be harnessed to enhance the efficiency of this astrocyte-neuron conversion process.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"189"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research progress of cysteine transporter SLC7A11 in endocrine and metabolic diseases.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-024-10193-5
Jiaqi Chen, Mengzhu Yuan, Jianping Wang
{"title":"Research progress of cysteine transporter SLC7A11 in endocrine and metabolic diseases.","authors":"Jiaqi Chen, Mengzhu Yuan, Jianping Wang","doi":"10.1007/s11033-024-10193-5","DOIUrl":"https://doi.org/10.1007/s11033-024-10193-5","url":null,"abstract":"<p><p>SLC7A11, often called xCT, belongs to the SLC family of transporters, which mediates the cellular influx of cystine and the efflux of glutamate. These transport processes are crucial for synthesizing GSH, enhancing the cell's ability to mitigate oxidative stress (OS). Emerging studies highlight the pivotal role of OS in triggering and exacerbating various metabolic and endocrine disorders, underlining the critical importance of regulating SLC7A11 expression levels. This study reviews the diverse roles of SLC7A11 in endocrine and metabolic diseases, examining its relationship with the metabolism of three key nutrients: proteins and amino acids, carbohydrates, and lipids. Additionally, the involvement of SLC7A11 in the onset and development of various common endocrine and metabolic disorders is analyzed. Additionally, it provides an overview of the current clinical and experimental use of SLC7A11 inhibitors and agonists. This review aims to offer insightful perspectives into the involvement of SLC7A11 in endocrine and metabolic pathologies and to foster the development of innovative therapeutic strategies that target SLC7A11.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"185"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple combinatorial interactions among natural structural variants of Brassica SOC1 promoters and SVP: conservation of binding affinity despite diversity in bimolecular interactions.
IF 2.6 4区 生物学
Molecular Biology Reports Pub Date : 2025-02-03 DOI: 10.1007/s11033-024-10182-8
Simran Kaur, Rinki Sisodia, Bharat Gupta, Kishor Gaikwad, Chaithanya Madhurantakam, Anandita Singh
{"title":"Multiple combinatorial interactions among natural structural variants of Brassica SOC1 promoters and SVP: conservation of binding affinity despite diversity in bimolecular interactions.","authors":"Simran Kaur, Rinki Sisodia, Bharat Gupta, Kishor Gaikwad, Chaithanya Madhurantakam, Anandita Singh","doi":"10.1007/s11033-024-10182-8","DOIUrl":"https://doi.org/10.1007/s11033-024-10182-8","url":null,"abstract":"<p><strong>Background: </strong>Analysis of binding patterns of biomolecules underpin new paradigms for trait engineering. One way of designing early flowering crops is to manipulate genes controlling flowering time. SOC1, a central integrator of flowering, is downregulated by SVP. In amphidiploid Brassica juncea, flowering is plausibly mediated by combinatorial interactions involving natural variants of SOC1 promoter and SVP protein homologs. Although fluctuating temperatures influence energetics of molecular interactions and phenotypes, mechanistic insights on these remain unknown. Herein, we report diversity in 50 homologs of SVP proteins from 25 Brassicaceae species.</p><p><strong>Materials and methods and results: </strong>Sequence and phylogenetic analysis of 9 natural variants of B. juncea SVP revealed differences in MIKC domains and sub-genome of origin. Generation and refinement of 15 SVP protein models (natural and hypothetical) using I-TASSER and ALPHAFOLD, and 3 SOC1 promoter fragments using 3D-DART, revealed structural diversity. Notwithstanding, binding affinity of 48 docked complexes analysed using HADDOCK and PreDBA were similar. Analysis of 27 docked complexes for distribution of shared or unique binding patterns and type of molecular contacts (π-π stacking, hydrophobic interactions, Van-der-Waals forces, H-bonds) using PyMOL, CCP4i, DNAproDB, PremPDI and DIMPLOT revealed extensive variation implicating compensatory mutations in preserving binding affinity. Yeast one-hybrid assays validated binding potential predicted in docked complexes. Conserved amino-acid and nucleotide residues involved in non-covalent interactions were identified. Computational alanine substitution established cruciality of amino-acid hotspots conferring stability to docked complexes.</p><p><strong>Conclusions: </strong>Our study is important as identification of crucial amino-acid hotspots is essential for rational protein design. Targeted mutagenesis resulting in modified binding spectrum of regulatory proteins suggests a way forward for trait engineering.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"187"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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