The Protein Journal最新文献

{"title":"Benjamin Widom (1930–2024) and the “∫”","authors":"Prakash Narayan, Mahesh Narayan","doi":"10.1007/s10930-026-10343-7","DOIUrl":"10.1007/s10930-026-10343-7","url":null,"abstract":"","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"613 - 614"},"PeriodicalIF":1.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Experimental and In-Silico Analysis Indicates Melittin as a Modulator of IL-37a-Associated Networks in Neuroblastoma","authors":"Berkay Ertan,&nbsp;Tugba Yalcinkaya,&nbsp;Elif Ercan,&nbsp;Ahmet Carhan","doi":"10.1007/s10930-026-10341-9","DOIUrl":"10.1007/s10930-026-10341-9","url":null,"abstract":"<div><p>Neuroinflammation is a key process that shapes tumor progression and cellular stress responses. While pro-inflammatory signaling components amplify these responses, IL-37a functions as an endogenous suppressor that limits inflammation. Melittin is a bioactive peptide with cytotoxic and immunomodulatory properties; however, its effects on IL-37a-centered immune regulation in neuroblastoma cells remain unclear. SH-SY5Y neuroblastoma cells were treated in vitro with melittin at concentrations of 1–32 µM for 24 and 48 h. Cell viability was assessed using the MTT assay. Expression levels of selected genes related to inflammation and extracellular matrix were analyzed by qRT-PCR. Targeted gene expression data were further used for protein–protein interaction network analysis, pathway enrichment analyses, and multivariate statistical approaches. In addition, potential interactions between melittin and STAT3 or IL-1R8 were evaluated by molecular docking, and ADMET properties were predicted. Melittin induced dose- and time-dependent cytotoxicity in SH-SY5Y cells, with an IC₅₀ value of 16 µM at 24 h. Melittin treatment led to a significant increase the expression of IL-37a, IL-18R1, and IL-1R8, while suppressing NF-κB, STAT3, MyD88, and Smad3. Caspase-1 expression was elevated, suggesting modulation of inflammation-associated cell death pathways. Extracellular matrix remodeling was differentially regulated, with increased MMP-2 and decreased MMP-9 expression. Multivariate analyses revealed a treatment-specific gene expression pattern. Molecular docking analyses suggested potential interactions between melittin and STAT3 or IL-1R8, while ADMET analysis indicated limited permeability and certain safety constraints. Melittin may emerge as a molecule that modulates inflammation-related gene expression in neuroblastoma cells and may be associated with IL-37a-related regulatory responses. These findings suggest that melittin could act as a potential modulator of inflammation-associated signaling pathways.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"558 - 575"},"PeriodicalIF":1.9,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Immunogenicity of Cood-Cotd, CfaB-st-CfaE, and Cssa-Cssb-ltb Chimeric Proteins and Their Chitosan Nanoparticles Against ETEC in an Animal Model","authors":"Behnam Zarei,&nbsp;Jafar Amani,&nbsp;Setareh Haghighat","doi":"10.1007/s10930-026-10342-8","DOIUrl":"10.1007/s10930-026-10342-8","url":null,"abstract":"<div><p>Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheal disease, and colonization factors together with enterotoxins are key targets for vaccine development. In this study, three ETEC-derived chimeric proteins, Cssa-Cssb-LTB, CfaB-ST-CfaE-LTB, and CooD-CotD, were produced and evaluated in free and chitosan nanoparticle-formulated forms. The recombinant proteins were expressed in E. coli BL21 (DE3) using the pET-28a vector, purified by Ni-NTA affinity chromatography, and confirmed by western blotting. Chitosan nanoparticles containing each recombinant protein were prepared and used for immunization of BALB/c mice. Antigen-specific antibody responses were assessed by ELISA. Cssa-Cssb-LTB was purified under soluble/native conditions, whereas CfaB-ST-CfaE-LTB and CooD-CotD were purified under denaturing conditions. The mean sizes of nanoparticles containing Cssa-Cssb-LTB, CfaB-ST-CfaE-LTB, and CooD-CotD were 121.5, 24.93, and 63.22 nm, respectively. Immunological evaluation showed that the cocktail formulation induced the strongest immune response, followed by the oral–injection regimen. The recombinant chimeric proteins induced marked humoral immune responses, and formulation in chitosan nanoparticles enhanced their immunogenic potential. These findings support the potential of chimeric antigen-loaded chitosan nanoparticles as a promising strategy for ETEC vaccine development.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"576 - 588"},"PeriodicalIF":1.9,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: In Memory of Prof. Alan George Marshall","authors":"Bruce E. Bursten,&nbsp;Lawrence J. Berliner","doi":"10.1007/s10930-026-10337-5","DOIUrl":"10.1007/s10930-026-10337-5","url":null,"abstract":"","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"615 - 615"},"PeriodicalIF":1.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148159703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Peptides: A Comprehensive Critical Review of Structure–Activity Relationships, Molecular Mechanisms, and Translational Limitations","authors":"Navneet Kumar Prasad,&nbsp;Rashmi Saxena Pal,&nbsp;Yogendra Pal,&nbsp;Sumedha Saxena,&nbsp;Priyanka Bhandari,&nbsp;Chandra Shekhar Tailor","doi":"10.1007/s10930-026-10339-3","DOIUrl":"10.1007/s10930-026-10339-3","url":null,"abstract":"<div><p>Bioactive peptides (BAPs) are short amino acid sequences released from precursor proteins through enzymatic hydrolysis, fermentation, or gastrointestinal digestion. Due to their diverse biological properties, BAPs have attracted significant attention for potential applications in functional foods, nutraceuticals, and therapeutic research. These peptides exhibit a wide range of activities, including antihypertensive, antioxidant, antimicrobial, anti-inflammatory, immunomodulatory, and anticancer effects, although the majority of current evidence remains derived from in vitro and preclinical studies. This comprehensive critical review summarises the major sources, production strategies, structural characteristics, and biological functions of food-derived bioactive peptides. Emphasis is placed on structure–activity relationships (SAR), residue-specific functional contributions, and molecular mechanisms underlying peptide bioactivity, including enzyme inhibition, membrane interaction, reactive oxygen species scavenging, and modulation of intracellular signalling pathways. In addition, the review critically evaluates translational and clinical limitations associated with bioactive peptides, including poor bioavailability, gastrointestinal instability, variability in peptide purification, and limited large-scale clinical validation. Comparative analytical synthesis further highlights the relationship between peptide sequence, structural features, and functional efficacy across different peptide classes. Overall, this comprehensive critical review provides an integrated synthesis of current evidence by combining structure–activity relationships (SAR) with mechanistic and translational insights, while highlighting major research gaps, clinical limitations, and future directions for peptide design, clinical evaluation, and functional food applications.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"521 - 548"},"PeriodicalIF":1.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Small Peptide Against Ischemic Fatty-Acid Binding Protein (FABP)","authors":"Harshita Shand,&nbsp;Soumendu Patra,&nbsp;Thirumurthy Madhavan,&nbsp;Suvankar Ghorai","doi":"10.1007/s10930-026-10338-4","DOIUrl":"10.1007/s10930-026-10338-4","url":null,"abstract":"<div><p>A low-molecular-weight cytoplasmic protein called heart-type fatty acid-binding protein (H-FABP) is released by cardiac myocytes during an ischemic episode. The normal serum level of FABP is around 3.5 ± 0.4 ng/ml (males), 3.9 ± 0.4 ng/ml (females), while the cutoff value of H-FABP in case of acute myocardial infarction (AMI) is 21.85 ng/ml within 3 hours. In case of angina pectoris, ischemic patients can be distinguished from non-ischemic patients and treated appropriately by detecting the presence of serum H-FABP in a point-of-care (POC) diagnostic approach. As the mortality rate due to coronary heart disease is on the rise worldwide, serum H-FABP levels can act as a diagnostic marker to assist in the prediction of probable cardiac arrest. In the present work, a small peptide against H-FABP has been screened by phage DNA library screening, which can be used for the development of a rapid and accurate diagnostic system for serum H-FABP. The cloning, expression and purification of the H-FABP protein in bacteria and screening of a 12 amino-acid long screened peptide with moderate affinity for binding to H-FABP is reported. The interaction of the said peptide with H-FABP was confirmed by in-silico methods like molecular docking and molecular dynamics simulation. The affinity of the peptide binding to H-FABP was assessed using Isothermal Titration Calorimetry (ITC). A spontaneous process is indicated by ΔG (-7.98 kcal mol⁻¹) values, but an endothermic interaction activity is implied by positive ΔH (3.11 kcal mol⁻¹) values. In a futuristic approach, this peptide can be exploited for the development of an accurate and early detection technique for heart ischemia.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 4","pages":"549 - 557"},"PeriodicalIF":1.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cloning, Expression, Purification and Biochemical Characterization of Novel Thermostable Subtilisin-like Serine Protease from Thermococcus onnurineus NA1","authors":"Nafiu Usman Jiddah,&nbsp;Ya’u Sabo Ajingi,&nbsp;Abubakar Sunusi Adam,&nbsp;Watanalai Panbangred,&nbsp;Petlada Dechayuenyong,&nbsp;Niporn Dejsuk,&nbsp;Nujarin Jongruja","doi":"10.1007/s10930-026-10336-6","DOIUrl":"10.1007/s10930-026-10336-6","url":null,"abstract":"<div><p>The persistent rise in demand for biocatalysts in industries has prompted the exploration of novel enzymes. Proteases are very important class of enzymes with many industrial applications. However, majority of the reported proteases are from mesophiles and exhibit low stability under harsh conditions limiting their potential applications. This study presents the expression and characterization of a novel thermostable recombinant subtilisin-like serine protease derived from <i>Thermococcus onnurineus</i> NA1. The subtilisin serine protease gene was successfully cloned and expressed in <i>E. coli</i> BL21. The recombinant protease was purified by affinity chromatography and has an estimated molecular mass of 29 kDa following SDS-PAGE analysis. It exhibited an optimal activity at a pH of 10 and temperature of 90 °C. The recombinant subtilisin-like serine protease maintained 96% of its activity at 100 °C. Additionally, Na⁺, Mg²⁺, Cu²⁺, and Mn²⁺ had minimal effect on the recombinant protease activity whereas the presence of Ca²⁺ significantly enhanced the enzyme activity. Interestingly, the recombinant protease was stable in the presence of different surfactants and inhibitors. These properties illustrate the potential of recombinant subtilisin-like serine protease for industrial applications.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 3","pages":"487 - 499"},"PeriodicalIF":1.4,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting oral squamous cell carcinoma with venom peptides: mechanisms, selectivity and translational potential","authors":"Vanitha Marunganathan,&nbsp;Imran Uddin","doi":"10.1007/s10930-026-10333-9","DOIUrl":"10.1007/s10930-026-10333-9","url":null,"abstract":"<div><p>Venom-derived peptides represent a promising new class of biotherapeutics for oral squamous cell carcinoma (OSCC), offering intrinsic tumor selectivity and multimodal anticancer activity that address key limitations of current chemoradiotherapy. By exploiting the aberrant biophysical features of OSCC cell membranes—including externalized anionic phospholipids, enhanced membrane fluidity, and microvilli-rich surface topology—cationic, amphipathic venom peptides preferentially bind to and disrupt malignant cells, triggering mitochondrial depolarization, reactive oxygen species generation, cytochrome‑c release, and caspase‑dependent apoptosis, alongside autophagy-associated death and regulated necrosis. Beyond direct cytotoxicity, these peptides modulate critical oncogenic pathways by inducing cell‑cycle arrest via cyclin-dependent kinase inhibition, targeting overexpressed ion channels, and suppressing epithelial–mesenchymal transition, extracellular matrix degradation, migration, and VEGF‑driven angiogenesis, thereby attenuating invasion and metastatic dissemination in OSCC models. Concurrently, selected venom peptides remodel the immunosuppressive tumor microenvironment through macrophage repolarization, dendritic-cell activation, enhancement of cytotoxic T‑cell responses, and interference with immune checkpoint signaling, linking rapid tumor debulking with more durable immune control. Recent advances in nanotechnology—including liposomes, polymeric and gold nanoparticles, chitosan-based systems, silica nanocarriers, and extracellular vesicles—have substantially improved venom peptide stability, pharmacokinetics, tumor-specific accumulation, and stimulus-responsive release, while mitigating systemic toxicity and hypersensitivity risks in preclinical OSCC models. However, translation to routine clinical practice still requires rigorous resolution of immunogenicity, off‑target effects, manufacturing scalability, and standardized dosing through well-designed, OSCC-focused preclinical studies and early-phase trials. Overall, this review positions venom-derived peptides not merely as cytolytic toxins but as a modular platform for precision, multi-targeted intervention in oral cancer, integrating direct membrane lysis, signaling reprogramming, anti-angiogenic and anti-metastatic effects, and onco-immunomodulation into a unified therapeutic strategy.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 3","pages":"461 - 478"},"PeriodicalIF":1.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Noncanonical Model of DED1 Interaction Betweenc-FLIPS and Procaspase-8","authors":"Zhuo Zhu,&nbsp;Zhi-Qiang Bai","doi":"10.1007/s10930-026-10335-7","DOIUrl":"10.1007/s10930-026-10335-7","url":null,"abstract":"<div><p>Procaspase-8 activation at the death-inducing signalling complex (DISC) is largely blocked by short c-FLIP isoforms (c-FLIP_S). The interaction between c-FLIP_S and procaspase-8 is mediated by their tandem death effector domains (tDED). The canonical model of tDED interaction suggests that c-FLIP_S uses H1a/H4a α helices of DED1 to interact with the H2b/H5b α helices of procaspase-8 DED2. Here, based on the NMR chemical shift perturbation of c-FLIP_S (F114G) resonances induced by titration with peptides derived from the helical regions of procaspase-8, a model structure of the c-FLIP_S:procaspase-8 complex was constructed using HADDOK. The complex revealed that their interactions are mediated by the two binding clefts on DED1 of c-FLIP_S and helices H1a/H4a of procaspase-8, the two clefts are formed by the α helices H1a, H5a, and H7a. The binding clefts on DED1 of c-FLIP_S were also suggested to bind nuclear factor kappa B (NF-κB) essential modulator (NEMO) and initiate NF-κB pathway activation. To further investigate the interaction between c-FLIP_S and NEMO, a c-FLIP_S:NEMO complex model was also constructed. Two complex structural models revealed that c-FLIP_S may interact with procaspase-8 and NEMO via a common binding surface. Furthermore, we hypothesized that c-FLIP_S uses a similar binding surface to interact with both procaspase-8 and NEMO, thereby promoting cell survival by inhibiting caspase-8 activation and inducing NF-κB activity.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 3","pages":"500 - 509"},"PeriodicalIF":1.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Scatchard Equation for a Multivalent Ligand: A Much Needed but Neglected Expression Required for Valid Interpretation of Biphasic Bioassays","authors":"Donald J. Winzor","doi":"10.1007/s10930-026-10334-8","DOIUrl":"10.1007/s10930-026-10334-8","url":null,"abstract":"<div><p>Attention is drawn to the availability of a version of the Scatchard expression that accommodates multivalence of the ligand. Its lack of application over the past four decades by biological researchers is surprising in view of the popularity of its univalent counterpart. This summary of its derivation and limited application presents published examples of situations where the curvilinearity of conventional Scatchard plots has been misinterpreted as signifying heterogeneity or negative cooperativity of binding sites on erythrocyte ghosts instead of tetravalence of glycolytic enzymes in their interaction with band 3 protein. Also presented is the rectangular hyperbolic relationship of which the generalized Scatchard expression is the linear transform.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"45 3","pages":"431 - 440"},"PeriodicalIF":1.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10930-026-10334-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}