Pub Date : 2026-05-01Epub Date: 2026-02-04DOI: 10.1016/j.bpc.2026.107590
Khaled M. Jami , Katherine E. Corbett , Daniel C. Farb , Kayla M. Osumi , Catelynn C. Shafer , Sophie Criscione , Dylan T. Murray
The loss of cellular proteostasis through aberrant stress granule formation is implicated in neurodegenerative diseases. Stress granules are formed by biomolecular condensation involving protein-protein and protein-RNA interactions. These assemblies are protective, but can rigidify, leading to amyloid-like fibril formation, a hallmark of the disease pathology. Key proteins dictating stress granule formation and disassembly, such as TDP43, contain low-complexity (LC) domains that drive fibril formation. HSPB8, a small heat shock protein, localizes to stress granules, has known aggregation delaying activity, and helps direct aggregated proteins to protein degradation pathways. It is not known how HSPB8 interacts with aggregation prone LC domains in stress granules. Here, we examine the interaction between isolated HSPB8 and the TDP43 LC using thioflavin T (ThT) and fluorescence polarization (FP) aggregation assays, fluorescence microscopy and photobleaching experiments, and crosslinking mass spectrometry (XL-MS). Our results indicate that HSPB8 delays TDP43 LC aggregation through domain-specific interactions with fibril nucleating species, without affecting fibril elongation rates. These findings provide mechanistic insight into how HSPB8 mediates LC domain aggregation and provides bases for investigating how the TDP43 LC subverts chaperone activity in neurodegenerative disease and comparing differing mechanisms between members of the HSPB protein family.
{"title":"Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation","authors":"Khaled M. Jami , Katherine E. Corbett , Daniel C. Farb , Kayla M. Osumi , Catelynn C. Shafer , Sophie Criscione , Dylan T. Murray","doi":"10.1016/j.bpc.2026.107590","DOIUrl":"10.1016/j.bpc.2026.107590","url":null,"abstract":"<div><div>The loss of cellular proteostasis through aberrant stress granule formation is implicated in neurodegenerative diseases. Stress granules are formed by biomolecular condensation involving protein-protein and protein-RNA interactions. These assemblies are protective, but can rigidify, leading to amyloid-like fibril formation, a hallmark of the disease pathology. Key proteins dictating stress granule formation and disassembly, such as TDP43, contain low-complexity (LC) domains that drive fibril formation. HSPB8, a small heat shock protein, localizes to stress granules, has known aggregation delaying activity, and helps direct aggregated proteins to protein degradation pathways. It is not known how HSPB8 interacts with aggregation prone LC domains in stress granules. Here, we examine the interaction between isolated HSPB8 and the TDP43 LC using thioflavin T (ThT) and fluorescence polarization (FP) aggregation assays, fluorescence microscopy and photobleaching experiments, and crosslinking mass spectrometry (XL-MS). Our results indicate that HSPB8 delays TDP43 LC aggregation through domain-specific interactions with fibril nucleating species, without affecting fibril elongation rates. These findings provide mechanistic insight into how HSPB8 mediates LC domain aggregation and provides bases for investigating how the TDP43 LC subverts chaperone activity in neurodegenerative disease and comparing differing mechanisms between members of the HSPB protein family.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"332 ","pages":"Article 107590"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fungal infections (mycoses) represent a significant and increasing global health concern, particularly in immunocompromised populations. The emergence of antifungal drug resistance and the limited efficacy of conventional treatments necessitate the development of novel therapeutic strategies. Antifungal peptides (AFPs), due to their broad-spectrum activity, low toxicity, and reduced likelihood of resistance development, have garnered considerable attention as potential alternatives. However, the experimental identification of AFPs remains costly, labor-intensive, and time-consuming. To address this challenge, we propose iAFP-fLRM, a hybrid deep learning framework for AFP prediction based solely on amino acid sequences. The model integrates BLOSUM62-based evolutionary features, token embeddings, positional embeddings, and a Transformer encoder, with a subsequent LSTM-ResMLP classification module to capture both global contextual.
information and local sequential dependencies. Notably, we design a dual-branch feature fusion module that integrates adaptive pooling alignment and cross-branch attention enhancement: the former dynamically aligns sequence lengths without information loss, while the latter adaptively adjusts the contribution of heterogeneous features to enhance complementarity. Extensive evaluations on benchmark datasets demonstrate that iAFP-fLRM achieves superior performance compared to state-of-the-art methods in terms of accuracy, the area under the receiver operating characteristic curve, and Matthews correlation coefficient. Ablation studies confirm the complementary effectiveness of combining handcrafted and learned features. Furthermore, t-SNE visualizations of the latent representations illustrate the model's ability to distinguish AFPs from non-AFPs. Overall, iAFP-fLRM provides a robust and scalable computational tool for in silico AFP identification, with the potential to facilitate antifungal peptide discovery and accelerate the development of novel antifungal therapeutics. The datasets and code used in this research are available at https://github.com/blue-tsuki/iAFP-fLRM.
{"title":"iAFP-fLRM: Accurate identification of antifungal peptides via hybrid deep learning architecture and multi-modal feature fusion","authors":"Shengli Zhang , Jianwei Cheng , Guixu Zhou , Jianhua Wang","doi":"10.1016/j.bpc.2026.107591","DOIUrl":"10.1016/j.bpc.2026.107591","url":null,"abstract":"<div><div>Fungal infections (mycoses) represent a significant and increasing global health concern, particularly in immunocompromised populations. The emergence of antifungal drug resistance and the limited efficacy of conventional treatments necessitate the development of novel therapeutic strategies. Antifungal peptides (AFPs), due to their broad-spectrum activity, low toxicity, and reduced likelihood of resistance development, have garnered considerable attention as potential alternatives. However, the experimental identification of AFPs remains costly, labor-intensive, and time-consuming. To address this challenge, we propose iAFP-fLRM, a hybrid deep learning framework for AFP prediction based solely on amino acid sequences. The model integrates BLOSUM62-based evolutionary features, token embeddings, positional embeddings, and a Transformer encoder, with a subsequent LSTM-ResMLP classification module to capture both global contextual.</div><div>information and local sequential dependencies. Notably, we design a dual-branch feature fusion module that integrates adaptive pooling alignment and cross-branch attention enhancement: the former dynamically aligns sequence lengths without information loss, while the latter adaptively adjusts the contribution of heterogeneous features to enhance complementarity. Extensive evaluations on benchmark datasets demonstrate that iAFP-fLRM achieves superior performance compared to state-of-the-art methods in terms of accuracy, the area under the receiver operating characteristic curve, and Matthews correlation coefficient. Ablation studies confirm the complementary effectiveness of combining handcrafted and learned features. Furthermore, t-SNE visualizations of the latent representations illustrate the model's ability to distinguish AFPs from non-AFPs. Overall, iAFP-fLRM provides a robust and scalable computational tool for in silico AFP identification, with the potential to facilitate antifungal peptide discovery and accelerate the development of novel antifungal therapeutics. The datasets and code used in this research are available at <span><span>https://github.com/blue-tsuki/iAFP-fLRM</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"332 ","pages":"Article 107591"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-02-04DOI: 10.1016/j.bpc.2026.107589
Neslihan Toyran , Feride Severcan
Biological membranes are complex structures whose structure and dynamics are modulated by various biomolecules, including ionic and sterol-like compounds. In this study, we investigated the molecular interactions of magnesium phosphate, in the absence and presence of vitamin D2, with simplified models of biological membranes composed of dipalmitoylphosphatidylcholine (DPPC). We aimed to elucidate their individual and combined effects on the order and dynamics (fluidity) of the hydrophobic part and the interfacial region using Fourier Transform Infrared (FTIR) spectroscopy. Our findings show that the phase transition temperature of the model membrane is not measurably affected by the presence of magnesium phosphate and/or vitamin D2. Our results also demonstrate that magnesium phosphate disrupts membrane integrity by decreasing the order of the pure DPPC and increasing the flexibility of the acyl chains in the deep interior of the bilayer, but, interestingly, it decreases membrane fluidity. These contradictory results on the order and dynamics of DPPC suggest a magnesium phosphate-induced phase separation in the membrane. Our findings also reveal that vitamin D2 enhances lipid order and reduces acyl chain mobility of the pure DPPC. In the joint presence of magnesium phosphate and vitamin D2, vitamin D2 counteracts the disordering effects of magnesium phosphate and restores membrane stability. Consequently, it abolishes the magnesium phosphate-induced phase separation. In addition, our findings reveal a decrease in the strength of hydrogen bonding in the interfacial region, which is explained by the presence of free carbonyl groups in all model membrane combinations. Overall, this study advances our understanding of how multivalent ion–phosphate species and hydrophobic micronutrients jointly regulate membrane organization, extending prior findings on free ion–vitamin D interactions to the less-explored case of magnesium phosphate.
{"title":"Magnesium phosphate-induced structural and dynamic modulation of model membranes in the presence and absence of vitamin D₂: Insights from FTIR analyses","authors":"Neslihan Toyran , Feride Severcan","doi":"10.1016/j.bpc.2026.107589","DOIUrl":"10.1016/j.bpc.2026.107589","url":null,"abstract":"<div><div>Biological membranes are complex structures whose structure and dynamics are modulated by various biomolecules, including ionic and sterol-like compounds. In this study, we investigated the molecular interactions of magnesium phosphate, in the absence and presence of vitamin D<sub>2,</sub> with simplified models of biological membranes composed of dipalmitoylphosphatidylcholine (DPPC). We aimed to elucidate their individual and combined effects on the order and dynamics (fluidity) of the hydrophobic part and the interfacial region using Fourier Transform Infrared (FTIR) spectroscopy. Our findings show that the phase transition temperature of the model membrane is not measurably affected by the presence of magnesium phosphate and/or vitamin D<sub>2</sub>. Our results also demonstrate that magnesium phosphate disrupts membrane integrity by decreasing the order of the pure DPPC and increasing the flexibility of the acyl chains in the deep interior of the bilayer, but, interestingly, it decreases membrane fluidity. These contradictory results on the order and dynamics of DPPC suggest a magnesium phosphate-induced phase separation in the membrane. Our findings also reveal that vitamin D<sub>2</sub> enhances lipid order and reduces acyl chain mobility of the pure DPPC. In the joint presence of magnesium phosphate and vitamin D<sub>2</sub>, vitamin D<sub>2</sub> counteracts the disordering effects of magnesium phosphate and restores membrane stability. Consequently, it abolishes the magnesium phosphate-induced phase separation. In addition, our findings reveal a decrease in the strength of hydrogen bonding in the interfacial region, which is explained by the presence of free carbonyl groups in all model membrane combinations. Overall, this study advances our understanding of how multivalent ion–phosphate species and hydrophobic micronutrients jointly regulate membrane organization, extending prior findings on free ion–vitamin D interactions to the less-explored case of magnesium phosphate.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"332 ","pages":"Article 107589"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-14DOI: 10.1016/j.bpc.2026.107578
Rani Mariam Cherian, C. Ravikumar
The title compound 3-(4-nitrophenyl)-3H-quinazolin-4-one (NPQ) was comprehensively characterized using FT-IR, Raman, and UV–vis spectroscopy. The compound was optimized in both solvent and gas phases using DFT/B3LYP method with 6–311++ G (d, p) as basis set. The calculated geometrical parameters and vibrational wavenumbers showed good agreement with the corresponding experimental results. Details about the charge density distribution and chemically reactive sites of the compound in both gas and solvent phase has been obtained by MEP mapping and Mulliken charge analysis. NBO analysis examines the unique charge transfer interactions inside the molecule. ELF and LOL investigations visualize localized and delocalized electrons in NPQ. The physical attributes ADMET (adsorption, distribution, metabolism, elimination, and toxicity) of the compound were calculated. The in vitro antibacterial activities of NPQ were studied and showed perceptible efficiency against E. coli and Pseudomonas aeruginosa. These experimental findings were supported with molecular docking studies which revealed strong binding energies and favorable interactions within the active site, suggesting a plausible mechanism for its antibacterial activity.
标题化合物3-(4-nitrophenyl)- 3h -quinazolin-4-one （NPQ）通过FT-IR、Raman和UV-vis光谱进行了全面表征。以6-311++ G （d, p）为基组，采用DFT/B3LYP法对化合物进行溶剂和气相优化。计算得到的几何参数和振动波数与实验结果吻合较好。通过MEP作图和Mulliken电荷分析，获得了化合物气相和溶剂相的电荷密度分布和化学反应位点的详细信息。NBO分析检查分子内独特的电荷转移相互作用。ELF和LOL研究可视化NPQ中的局域和非局域电子。计算了化合物的物理属性ADMET（吸附、分布、代谢、消除和毒性）。研究了NPQ的体外抑菌活性，对大肠杆菌和铜绿假单胞菌均有明显的抑菌效果。这些实验结果得到了分子对接研究的支持，发现活性位点具有强结合能和良好的相互作用，这可能是其抗菌活性的合理机制。
{"title":"Spectroscopic, quantum chemical, and antibacterial studies on novel push–pull chromophore 3-(4-nitrophenyl)-3H-quinazolin-4-one","authors":"Rani Mariam Cherian, C. Ravikumar","doi":"10.1016/j.bpc.2026.107578","DOIUrl":"10.1016/j.bpc.2026.107578","url":null,"abstract":"<div><div>The title compound 3-(4-nitrophenyl)-3H-quinazolin-4-one (NPQ) was comprehensively characterized using FT-IR, Raman, and UV–vis spectroscopy. The compound was optimized in both solvent and gas phases using DFT/B3LYP method with 6–311++ G (d, p) as basis set. The calculated geometrical parameters and vibrational wavenumbers showed good agreement with the corresponding experimental results. Details about the charge density distribution and chemically reactive sites of the compound in both gas and solvent phase has been obtained by MEP mapping and Mulliken charge analysis. NBO analysis examines the unique charge transfer interactions inside the molecule. ELF and LOL investigations visualize localized and delocalized electrons in NPQ. The physical attributes ADMET (adsorption, distribution, metabolism, elimination, and toxicity) of the compound were calculated. The <em>in vitro</em> antibacterial activities of NPQ were studied and showed perceptible efficiency against <em>E. coli</em> and <em>Pseudomonas aeruginosa</em>. These experimental findings were supported with molecular docking studies which revealed strong binding energies and favorable interactions within the active site, suggesting a plausible mechanism for its antibacterial activity.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107578"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-14DOI: 10.1016/j.bpc.2026.107579
Mohtashim Lohani , Nizar Ahmad Khamjan , Sajad Ahmad Dar , Farrukh Aqil , Saif Khan , Arshad Jawed , Saba Beigh , Iffat Zareen Ahmad
Vitamin D is critical for calcium homeostasis, bone health, and immune regulation via the Vitamin D Receptor. Mutations in the ligand-binding domain and DNA-binding domain can disrupt ligand interactions, causing biologically active metabolite of vitamin D [1α,25-dihydroxyvitamin D3 (calcitriol)] resistance and clinical complications such as hereditary rickets and immune dysregulation. This study explored the structural and functional effects of VDR missense mutations using computational approaches. An AlphaFold-generated VDR model incorporated selected mutations from 503 reported variants, of which 62 were likely pathogenic. Ten LBD mutations were analyzed. Molecular docking assessed Vitamin D3 binding, while molecular dynamics simulations, Root Mean Square Deviation, Radius of Gyration, and Principal Component Analysis evaluated structural stability. CASTp analyses identified key residues in the binding pocket, and downstream non-genomic pathways were assessed to interpret functional effects. Mutations R → H and R → L at position 274, and H → Q at position 305, exhibited minimal RMSD and Rg fluctuations, indicating stable protein conformations. Docking revealed reduced binding affinities (−8.9, −8.8, −9.0 kcal/mol) relative to wild-type (−9.9 kcal/mol), suggesting altered ligand-binding geometry. Other mutations showed greater structural deviations, indicating potential impairment of receptor function. Functional analysis suggested disruption of signaling essential for calcium homeostasis, bone mineralization, and immune regulation. These results demonstrate that missense mutations in the VDR LBD compromise Vitamin D3 binding and receptor stability, contributing to resistance and related skeletal and immune abnormalities. Computational modeling offers a framework to identify pathogenic variants and guide therapeutic strategies, including small molecules, peptide therapies, CRISPR-Cas9 editing, or Vitamin D analogs to restore receptor function and improve clinical outcomes.
{"title":"Structural and functional insights into Vitamin D receptor mutations: An in-silico investigation of polymorphism-induced resistance","authors":"Mohtashim Lohani , Nizar Ahmad Khamjan , Sajad Ahmad Dar , Farrukh Aqil , Saif Khan , Arshad Jawed , Saba Beigh , Iffat Zareen Ahmad","doi":"10.1016/j.bpc.2026.107579","DOIUrl":"10.1016/j.bpc.2026.107579","url":null,"abstract":"<div><div>Vitamin D is critical for calcium homeostasis, bone health, and immune regulation via the Vitamin D Receptor. Mutations in the ligand-binding domain and DNA-binding domain can disrupt ligand interactions, causing biologically active metabolite of vitamin D [1α,25-dihydroxyvitamin D3 (calcitriol)] resistance and clinical complications such as hereditary rickets and immune dysregulation. This study explored the structural and functional effects of VDR missense mutations using computational approaches. An AlphaFold-generated VDR model incorporated selected mutations from 503 reported variants, of which 62 were likely pathogenic. Ten LBD mutations were analyzed. Molecular docking assessed Vitamin D3 binding, while molecular dynamics simulations, Root Mean Square Deviation, Radius of Gyration, and Principal Component Analysis evaluated structural stability. CASTp analyses identified key residues in the binding pocket, and downstream non-genomic pathways were assessed to interpret functional effects. Mutations R → H and R → L at position 274, and H → Q at position 305, exhibited minimal RMSD and Rg fluctuations, indicating stable protein conformations. Docking revealed reduced binding affinities (−8.9, −8.8, −9.0 kcal/mol) relative to wild-type (−9.9 kcal/mol), suggesting altered ligand-binding geometry. Other mutations showed greater structural deviations, indicating potential impairment of receptor function. Functional analysis suggested disruption of signaling essential for calcium homeostasis, bone mineralization, and immune regulation. These results demonstrate that missense mutations in the VDR LBD compromise Vitamin D3 binding and receptor stability, contributing to resistance and related skeletal and immune abnormalities. Computational modeling offers a framework to identify pathogenic variants and guide therapeutic strategies, including small molecules, peptide therapies, CRISPR-Cas9 editing, or Vitamin D analogs to restore receptor function and improve clinical outcomes.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107579"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-22DOI: 10.1016/j.bpc.2026.107580
M.O. Ershova, A.A. Valueva, T.O. Pleshakova
An approach to evaluate the efficiency of aptamer/antigen complexation based on high-resolution AFM imaging data is proposed. The formation of specific complexes is the basis of diagnostic systems in medicine. It is shown that a comprehensive evaluation of the height and volume of objects sorbed on the surface of freshly cleaved mica from the solution of proteins and their complexes allows us to assess the success of complex formation in solution. The applicability of the approach is demonstrated using two variants of the CA125 antigen (containing seven or one full-length SEA domain) and two aptamers. The SEA domain is the binding contact in the antibody- or aptamer-mediated biorecognition system.
{"title":"High-resolution AFM imaging of the CA125 protein and its aptamer-based complexes","authors":"M.O. Ershova, A.A. Valueva, T.O. Pleshakova","doi":"10.1016/j.bpc.2026.107580","DOIUrl":"10.1016/j.bpc.2026.107580","url":null,"abstract":"<div><div>An approach to evaluate the efficiency of aptamer/antigen complexation based on high-resolution AFM imaging data is proposed. The formation of specific complexes is the basis of diagnostic systems in medicine. It is shown that a comprehensive evaluation of the height and volume of objects sorbed on the surface of freshly cleaved mica from the solution of proteins and their complexes allows us to assess the success of complex formation in solution. The applicability of the approach is demonstrated using two variants of the CA125 antigen (containing seven or one full-length SEA domain) and two aptamers. The SEA domain is the binding contact in the antibody- or aptamer-mediated biorecognition system.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107580"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-08DOI: 10.1016/j.bpc.2026.107574
Abid Ali, Mikhail Matveyenka, Dmitry Kurouski
Transthyretin (TTR) is a tetrameric transporter of retinol and thyroxine that aggregates in the central and peripheral nervous system upon a severe pathology known as transthyretin amyloidosis. Although small molecular weight drugs can stabilize TTR preventing its aggregation, molecular mechanisms of transthyretin amyloidosis remain poorly understood. Accumulating evidence indicates that lipids can alter TTR stability by facilitating protein aggregation into toxic oligomers and fibrils. Consequently, pathological changes in the lipid composition of plasma membranes can be responsible for the onset and progression of transthyretin amyloidosis. In this study, we investigated the role of concentration-dependent changes in phosphatidylcholine (PC), one of the most abundant phospholipids in the plasma membrane, on the rate of TTR aggregation. For this, TTR was exposed to large unilamellar vesicles (LUVs) composed of 30%, 35%, and 40% PC. We found that a decrease in the concentration of PC from 40% to 35% drastically accelerated TTR aggregation. We also observed an increase in the cytotoxicity of TTR aggregates formed in the presence of 35% PC compared to TTR fibrils grown in the presence of LUVs with 40% PC. These results indicate that changes in the concentration of PC in the plasma membrane could trigger amyloid formation that leads to transthyretin amyloidosis.
{"title":"Changes in the concentration of phosphatidylcholine in lipid bilayers determines the aggregation rate of transthyretin","authors":"Abid Ali, Mikhail Matveyenka, Dmitry Kurouski","doi":"10.1016/j.bpc.2026.107574","DOIUrl":"10.1016/j.bpc.2026.107574","url":null,"abstract":"<div><div>Transthyretin (TTR) is a tetrameric transporter of retinol and thyroxine that aggregates in the central and peripheral nervous system upon a severe pathology known as transthyretin amyloidosis. Although small molecular weight drugs can stabilize TTR preventing its aggregation, molecular mechanisms of transthyretin amyloidosis remain poorly understood. Accumulating evidence indicates that lipids can alter TTR stability by facilitating protein aggregation into toxic oligomers and fibrils. Consequently, pathological changes in the lipid composition of plasma membranes can be responsible for the onset and progression of transthyretin amyloidosis. In this study, we investigated the role of concentration-dependent changes in phosphatidylcholine (PC), one of the most abundant phospholipids in the plasma membrane, on the rate of TTR aggregation. For this, TTR was exposed to large unilamellar vesicles (LUVs) composed of 30%, 35%, and 40% PC. We found that a decrease in the concentration of PC from 40% to 35% drastically accelerated TTR aggregation. We also observed an increase in the cytotoxicity of TTR aggregates formed in the presence of 35% PC compared to TTR fibrils grown in the presence of LUVs with 40% PC. These results indicate that changes in the concentration of PC in the plasma membrane could trigger amyloid formation that leads to transthyretin amyloidosis.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107574"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-23DOI: 10.1016/j.bpc.2026.107582
Arindam Das , Shukdeb Sing , Gouranga Jana , Anirban Basu
Anti-amyloidogenic potential of tomato extract was explored using hen egg white lysozyme as model protein. Total polyphenolic content was determined to ensure the reported bio-activeness of tomato extract. Various spectroscopic and microscopic methods were employed to assess its anti-amyloidogenic property. Thioflavin T and congo red assays revealed dose dependent inhibition of lysozyme amyloid fibrillation. Furthermore, nile red and 8-anilino-1-naphthalenesulfonic acid assays confirmed less alteration in protein surface hydrophobicity during fibrillation in presence of tomato extract. Intrinsic fluorescence measurement also supported a steady reduction in fibril formation in presence of the tomato extract. Atomic force microscopic imaging clearly demonstrated that tomato extract significantly mitigated lysozyme fibrillation.
{"title":"Assessing the inhibitory effect of lyophilised tomato extract on lysozyme fibrillation: Spectrochemical and microscopic analysis","authors":"Arindam Das , Shukdeb Sing , Gouranga Jana , Anirban Basu","doi":"10.1016/j.bpc.2026.107582","DOIUrl":"10.1016/j.bpc.2026.107582","url":null,"abstract":"<div><div>Anti-amyloidogenic potential of tomato extract was explored using hen egg white lysozyme as model protein. Total polyphenolic content was determined to ensure the reported bio-activeness of tomato extract. Various spectroscopic and microscopic methods were employed to assess its anti-amyloidogenic property. Thioflavin T and congo red assays revealed dose dependent inhibition of lysozyme amyloid fibrillation. Furthermore, nile red and 8-anilino-1-naphthalenesulfonic acid assays confirmed less alteration in protein surface hydrophobicity during fibrillation in presence of tomato extract. Intrinsic fluorescence measurement also supported a steady reduction in fibril formation in presence of the tomato extract. Atomic force microscopic imaging clearly demonstrated that tomato extract significantly mitigated lysozyme fibrillation.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107582"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-20DOI: 10.1016/j.bpc.2026.107581
Sayan Karmakar, Parbati Biswas
Carbon nanotubes possess multi-functional characteristics due to their unique physiochemical properties. All atom, explicit-solvent molecular dynamics simulations is used to explore the conformations of the polyglutamate chains of different lengths and its surface interactions with single walled carbon nanotubes of different diameters. The adsorption of the polyglutamate chains on the surface of these carbon nanotubes is governed by two critical ratios that depends on the geometric parameters of the polyglutamate chains and the carbon nanotubes. The -helical content of the polyglutamate chains decreases with the increase in diameter of the carbon nanotubes. The number of intramolecular hydrogen bonds in the polyglutamate chains decrease upon adsorption on the surface of the nanotubes as compared to those in its absence. Polyglutamate adsorption on carbon nanotubes is largely due to van der Waals interactions. Shorter polyglutamate chains are more prone to adsorption. The distribution of water molecules for the adsorbed polyglutamate chains show that adsorption is governed by hydrophilic interactions.
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Pub Date : 2026-04-01Epub Date: 2026-01-12DOI: 10.1016/j.bpc.2026.107577
Tina Jacob , Wolfgang Hoyer
Liquid–liquid phase separation (LLPS) of proteins implicated in neurodegenerative diseases has gained growing attention in recent years, due to its potential role in driving the transition from functional protein monomers to pathogenic aggregates. However, the mechanisms by which phase separation contributes to the loss of protein function and promotes aggregation remain poorly understood. Recent studies show that multiple proteins or other biomolecules can colocalize within the biomolecular condensates, creating a highly interactive microenvironment that can modulate aggregation. In this review we look into the heterotypic phase separation of tau and α-synuclein, the two key proteins responsible for critical neurodegenerative disorders. By compiling recent findings, this review highlights the modulatory role of heterotypic condensates in disease progression and aims to provide an alternative perspective on regulation of protein aggregation in neurodegeneration.
{"title":"Heterotypic phase separation in aggregation: Driver or deterrent?","authors":"Tina Jacob , Wolfgang Hoyer","doi":"10.1016/j.bpc.2026.107577","DOIUrl":"10.1016/j.bpc.2026.107577","url":null,"abstract":"<div><div>Liquid–liquid phase separation (LLPS) of proteins implicated in neurodegenerative diseases has gained growing attention in recent years, due to its potential role in driving the transition from functional protein monomers to pathogenic aggregates. However, the mechanisms by which phase separation contributes to the loss of protein function and promotes aggregation remain poorly understood. Recent studies show that multiple proteins or other biomolecules can colocalize within the biomolecular condensates, creating a highly interactive microenvironment that can modulate aggregation. In this review we look into the heterotypic phase separation of tau and α-synuclein, the two key proteins responsible for critical neurodegenerative disorders. By compiling recent findings, this review highlights the modulatory role of heterotypic condensates in disease progression and aims to provide an alternative perspective on regulation of protein aggregation in neurodegeneration.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"331 ","pages":"Article 107577"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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