Biochimica et biophysica acta. Biomembranes最新文献_第6页

The molecular electrometer at 40 分子静电计在40。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI: 10.1016/j.bbamem.2025.184453

Peter M. Macdonald

{"title":"The molecular electrometer at 40","authors":"Peter M. Macdonald","doi":"10.1016/j.bbamem.2025.184453","DOIUrl":"10.1016/j.bbamem.2025.184453","url":null,"abstract":"<div><div>In 1987 Seelig and colleagues proposed that the phosphocholine headgroup of phosphatidylcholine behaved as a universal sensor of surface electrostatic charge, both cationic and anionic, in lipid bilayers (J. Seelig, P.M. Macdonald, P.G. Scherer, Phospholipid Head Groups as Sensors of Electric Charge in Membranes<em>.</em> Biochemistry, 26 (1987) 7535–7541.) Changes in the deuterium NMR quadrupolar splitting measured with specifically-deuterated positions within the choline headgroup in response to surface charges were attributed to a conformational change within the phosphocholine group corresponding to a “tilt” of the choline group towards or away from the direction of the bilayer normal as the P<img>N dipole sought to align with the surface electrostatic field. In the ensuing nearly 4 decades this so-called “Molecular Electrometer” concept has become accepted doctrine in membrane science and has been employed to examine lipid bilayer surface electrostatics in a host of situations involving multiple membrane- associating biologically significant factors from ions, to anesthetics, to peptides and proteins. In this review, I describe the history of the science behind the Molecular Electrometer, the evolution of methods for examining the Molecular Electrometer response and provide a survey of its application in the myriad instances of membrane-associating molecules affecting and being affected by surface electrostatics. Lastly, I include an overview of the efforts of molecular dynamics simulations to be guided by and to account for the Molecular Electrometer effect in simulations of lipid bilayers.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184453"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032584","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}

引用次数: 0

Study on the correlation between proton transfer of phenolic hydroxyl groups of 6 flavonoid compounds and their antioxidant activities 6种黄酮类化合物酚羟基质子转移与抗氧化活性的相关性研究

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-12-01 Epub Date: 2025-08-19 DOI: 10.1016/j.bbamem.2025.184444

Shuangmei Gong , Changying Yang , Min Li , Xiaobo Li

引用次数: 0

Improving chemical synthesis and the antimicrobial activity of human defensins through disulfide bond engineering of HBD-3 利用HBD-3的二硫键工程技术提高人体防御素的化学合成和抗菌活性

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.bbamem.2025.184457

Aleksandra Walewska , Paulina Kosikowska-Adamus , Anna Wardowska , Grzegorz Bulaj , Emilia Sikorska

{"title":"Improving chemical synthesis and the antimicrobial activity of human defensins through disulfide bond engineering of HBD-3","authors":"Aleksandra Walewska , Paulina Kosikowska-Adamus , Anna Wardowska , Grzegorz Bulaj , Emilia Sikorska","doi":"10.1016/j.bbamem.2025.184457","DOIUrl":"10.1016/j.bbamem.2025.184457","url":null,"abstract":"<div><div>Human β-defensins are disulfide-rich peptides that exhibit broad-spectrum antimicrobial activity against bacteria, fungi, and certain viruses, while also exerting immunomodulatory effects. As naturally occurring host defense peptides in the human body, they are less likely to induce adverse immune reactions or toxicity compared to synthetic drugs. Efficient chemical synthesis of cysteine-rich peptides is critical for drug lead optimization studies, yet in many cases is limiting by the low yields of correctly formed disulfide bonds. Herein, we present novel β-defensin 3 analogues with engineered disulfide bonds, designed to simplify and improve oxidative folding while preserving antimicrobial and antifungal activities. Our results suggest that the judicious replacement of cysteine residues with alanines or selenocysteines may facilitate the development of defensin-based drug leads with enhanced pharmacological properties, addressing their therapeutic potential to combat multidrug resistance.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184457"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046027","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}

引用次数: 0

Small angle neutron scattering study of rhodopsin oligomerization and G-protein coupling in a physiologically relevant lipid membrane 生理相关脂质膜中紫红质寡聚和g蛋白偶联的小角中子散射研究。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-12-01 Epub Date: 2025-09-11 DOI: 10.1016/j.bbamem.2025.184454

Olivier Soubias , Jonathan D. Nickels , Kirk G. Hines , Walter E. Teague , John K. Northup , John Katsaras , Klaus Gawrisch

{"title":"Small angle neutron scattering study of rhodopsin oligomerization and G-protein coupling in a physiologically relevant lipid membrane","authors":"Olivier Soubias , Jonathan D. Nickels , Kirk G. Hines , Walter E. Teague , John K. Northup , John Katsaras , Klaus Gawrisch","doi":"10.1016/j.bbamem.2025.184454","DOIUrl":"10.1016/j.bbamem.2025.184454","url":null,"abstract":"<div><div>Although the oligomeric states of G-protein-coupled receptors (GPCRs) and interactions with cognate G proteins are central to their signal transduction capabilities, they remain poorly defined. In this study, we used small-angle neutron scattering (SANS) and a neutron contrast matching approach to elucidate the oligomeric states of the archetypal GPCR, rhodopsin, and its interaction with the G protein transducin (G<sub>t</sub>). At a rhodopsin/lipid molar ratio of 1/360, we found that dark-adapted rhodopsin exists as a monomer, a finding consistent with its high functional activity measured upon photoactivation by spectrophotometry and the rate of catalyzed [<sup>35</sup>S]-GTP-γ-S exchange. Following light activation, we observed that rhodopsin forms a stable 1:1 stoichiometric complex with G<sub>t</sub>, the structure of which is consistent with recent cryo-EM data. In contrast, activated rhodopsin in the absence of G<sub>t</sub> showed a propensity to form higher order oligomers. This research underscores the concentration-dependent nature of rhodopsin oligomerization and establishes SANS and the ability to produce appropriately contrast-matched samples, as a robust strategy for characterizing integral membrane protein interactions under biologically relevant conditions.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184454"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058243","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}

引用次数: 0

Novel flavonoid-magnesium complexes as inhibitors of plasma membrane calcium ATPase 新型类黄酮-镁复合物作为质膜钙atp酶抑制剂

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI: 10.1016/j.bbamem.2025.184438

Mallku Q. Ontiveros , Mariel Marder , Rolando C. Rossi , Juan Pablo Rossi , Irene C. Mangialavori , Mariela S. Ferreira-Gomes

{"title":"Novel flavonoid-magnesium complexes as inhibitors of plasma membrane calcium ATPase","authors":"Mallku Q. Ontiveros , Mariel Marder , Rolando C. Rossi , Juan Pablo Rossi , Irene C. Mangialavori , Mariela S. Ferreira-Gomes","doi":"10.1016/j.bbamem.2025.184438","DOIUrl":"10.1016/j.bbamem.2025.184438","url":null,"abstract":"<div><div>Plasma membrane calcium ATPases (PMCAs) are essential for regulating intracellular calcium (Ca<sup>2+</sup>) levels by extruding it from the cytosol. Improper regulation of these transporters is associated with numerous diseases, including neurological, cardiovascular, oncological, and metabolic problems, rendering them interesting targets for therapeutic intervention. However, there is a scarcity of specific tools to adjust PMCA activity. Flavonoids, a varied group of polyphenolic compounds with numerous biological effects, have been demonstrated to affect the function of several ATPases, including PMCAs.</div><div>In this study, we investigated the inhibitory mechanism of quercetin on the human PMCA4 isoform (hPMCA4). Using UV–visible spectroscopy and ATPase activity assay, we identified a high-affinity inhibition mediated by a quercetin‑magnesium (Mg<sup>2+</sup>) complex with a Ki of 49.7 ± 1.5 nM. Functional and phosphorylation studies at different pHs suggest that quercetin affects PMCA activity through two inhibitory mechanisms: a high-affinity one mediated by the quercetin-Mg<sup>2+</sup> complex and a low-affinity one mediated by the free flavonoid.</div><div>Analysis of the structure-activity relationship revealed that hydroxyl groups at positions 3′, 4′, and 3 are critical for complex formation and inhibitory potency. Specifically, the 3′ and 4′ hydroxyls are required to form the PMCA inhibitory complex. These findings demonstrate a novel mechanism of PMCA activity modulation involving flavonoid-Mg<sup>2+</sup> complexes, which emerge as selective molecular tools capable of regulating Ca<sup>2+</sup> transport. This knowledge provides new insights into designing PMCA inhibitors and exploring therapeutic strategies targeting diseases linked to calcium signalling dysfunction.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 7","pages":"Article 184438"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780900","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}

引用次数: 0

Rescue of sirtuin inhibitor-dependent decrease in claudin-4 expression and paracellular barrier property in keratinocytes by epigallocatechin gallate 没食子儿茶素没食子酸酯对sirtuin抑制剂依赖性的角化细胞claudin-4表达降低和细胞旁屏障特性的拯救作用

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.bbamem.2025.184440

Maika Miwa , Miki Tanabe , Shunsuke Matsuda , Kento Yamakawa , Yuta Yoshino , Norihiro Tada , Akichika Itoh , Akira Ikari

{"title":"Rescue of sirtuin inhibitor-dependent decrease in claudin-4 expression and paracellular barrier property in keratinocytes by epigallocatechin gallate","authors":"Maika Miwa , Miki Tanabe , Shunsuke Matsuda , Kento Yamakawa , Yuta Yoshino , Norihiro Tada , Akichika Itoh , Akira Ikari","doi":"10.1016/j.bbamem.2025.184440","DOIUrl":"10.1016/j.bbamem.2025.184440","url":null,"abstract":"<div><div>The barrier function of granular layer in the skin is mainly sustained by claudin-1 (CLDN1) and CLDN4, tight junctional components. We recently found that the activity of sirtuin-2 (SIRT2), an anti-aging molecule, is decreased with aging in keratinocytes, leading to the attenuation of CLDN4 expression and paracellular barrier function. SIRT2 may be a novel target for enhancing skin barrier function in elderly people. <em>In vitro</em> SIRT2 activity assay showed that epigallocatechin gallate (EGCG) and green tea extract (GT) have a potent ability to activate SIRT2. Tenovin-1 (Ten-1), a sirtuin-1/2 inhibitor, decreased the SIRT2 activity in human keratinocyte-derived HaCaT cells, which was rescued by EGCG and GT. Ten-1 decreased the protein level of CLDN4, which was rescued by EGCG, whereas CLDN1 expression was changed by neither Ten-1 nor EGCG. Ten-1 decreased the tight junctional localization of CLDN4, transepithelial electrical resistance, and paracellular permeability to FD4, a fluorescence paracellular flux marker, which were rescued by EGCG. Ten-1 increased the acetylation level of CLDN4, which was inhibited by EGCG without affecting NAD<sup>+</sup> content, a substrate for SIRT2. The protein levels of wild-type and K191A mutant were decreased by Ten-1, whereas that of K196A was not. Furthermore, Ten-1 increased the acetylation levels of WT and K191A mutant. We suggest that Ten-1 decreases CLDN4 expression mediated by the acetylation of K196 of CLDN4 and EGCG is useful to protect from aging-induced dysfunction of paracellular barrier in the keratinocytes.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 7","pages":"Article 184440"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781745","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}

引用次数: 0

Two phase coexistence in ternary mixtures of saturated and polyunsaturated phosphatidylcholines with cholesterol. 饱和和多不饱和磷脂酰胆碱与胆固醇三元混合物的两相共存。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.bbamem.2025.184436

James H Davis

引用次数: 0

The phospholipolytically active neurotoxin Vipoxin induces changes of the mechanical properties of breast epithelial cells 磷脂多活性神经毒素Vipoxin诱导乳腺上皮细胞力学特性的改变。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-07-09 DOI: 10.1016/j.bbamem.2025.184434

Will Linthicum , Qi Wen , Nancy A. Burnham , Svetla D. Petrova , Konstantin Balashev

{"title":"The phospholipolytically active neurotoxin Vipoxin induces changes of the mechanical properties of breast epithelial cells","authors":"Will Linthicum , Qi Wen , Nancy A. Burnham , Svetla D. Petrova , Konstantin Balashev","doi":"10.1016/j.bbamem.2025.184434","DOIUrl":"10.1016/j.bbamem.2025.184434","url":null,"abstract":"<div><div>The investigation of how drugs or toxins alter cell mechanics is gaining significant traction in biomedical science, driven by the dual objectives of elucidating their mechanisms of action and enhancing drug screening processes. In this study, Atomic Force Microscopy (AFM), a prominent experimental technique in recent years, was employed to examine and analyze the mechanical responses of cells exposed to the neurotoxin Vipoxin. This method enables the precise measurement of key mechanical parameters such as cell stiffness and viscoelasticity before and after toxin introduction in the cell culture. It was demonstrated that the cells' stiffness and viscosity decreased with increasing Vipoxin concentration. Additionally, Total Internal Reflection Fluorescence Microscopy (TIRFM) was utilized to monitor morphological changes in the cells over time. These morphological changes were quantitatively analyzed using fractal analysis of the acquired images. The observed changes in cell shapes implied the reorganization of the cell cytoskeleton, thus providing insight into a comprehensive understanding of cell mechanics under the influence of Vipoxin.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 7","pages":"Article 184434"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616113","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}

引用次数: 0

Development of amyloid-cationic peptides with antimicrobial activities: Relation to their membranotropic activities. 具有抗菌活性的淀粉样阳离子肽的开发：与其膜性活性的关系。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.bbamem.2025.184439

Marta Balestra, Lilia Leghmizi, Thierry Drujon, Loïc Portier, Cillian Byrne, Fabienne Burlina, Sylvie Noinville

{"title":"Development of amyloid-cationic peptides with antimicrobial activities: Relation to their membranotropic activities.","authors":"Marta Balestra, Lilia Leghmizi, Thierry Drujon, Loïc Portier, Cillian Byrne, Fabienne Burlina, Sylvie Noinville","doi":"10.1016/j.bbamem.2025.184439","DOIUrl":"10.1016/j.bbamem.2025.184439","url":null,"abstract":"<p><p>We describe here a new class of antimicrobial peptides (named Amy-Cat) comprised of a short amyloid domain and a cationic domain, as a primary amphipathic structure. The nona-arginine sequence was chosen as the cationic motif, while the sequence and size of the amyloid domain was modulated. The Amy-Cat peptides were found to be bactericidal against gram-negative and gram-positive standard bacterial strains with minimum inhibitory concentrations ranging from 3 to 24 μM, and being well-below their hemolytic concentrations. Their membranotropic activities were investigated as a function of the amyloid sequence and compared to those of the nona-arginine peptide. Calcein dye leakage on lipid mimic models for bacterial and eukaryotic membranes was carried out. In addition, the effect of the amyloid moiety on the membrane binding and on the conformational change were investigated at the buffer/supported lipid bilayer interface using ATR-FTIR spectroscopy. The overall findings suggest optimum routes to balancing the hydrophobicity of the amyloid sequence over the fixed cationic sequence allowing selective disruption of the bacterial membranes without eliciting hemolysis. Amy-Cat peptides appear to be very promising candidates for the development of new antimicrobial agents.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184439"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811670","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}

引用次数: 0

Assessing the anticancer potential of spider venom peptide Latarcin Ltc2a against triple negative breast cancer 评估蜘蛛毒液肽Latarcin Ltc2a对三阴性乳腺癌的抗癌潜力

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1016/j.bbamem.2025.184442

Prasanjeet Kaur , Srabaita Roy , Shilpi Minocha , Archana Chugh

{"title":"Assessing the anticancer potential of spider venom peptide Latarcin Ltc2a against triple negative breast cancer","authors":"Prasanjeet Kaur , Srabaita Roy , Shilpi Minocha , Archana Chugh","doi":"10.1016/j.bbamem.2025.184442","DOIUrl":"10.1016/j.bbamem.2025.184442","url":null,"abstract":"<div><div>Cancer remains one of the most formidable challenges to human health, necessitating constant exploration of innovative therapeutic strategies. Among the myriad potential candidates, peptides from venom have emerged as potent sources of bioactive molecules possessing diverse pharmacological properties. In this study, we repurposed a spider venom-derived antimicrobial peptide, Ltc2a, into a selective anticancer agent, bridging microbial defense with cancer therapeutics. Our findings reveal that Ltc2a exhibits selective cytotoxicity towards cancer cells compared to normal cells at just 2 μM of the peptide concentration. Ltc2a induced rapid cytotoxicity within 1 h in breast cancer cells and it was accompanied by membrane disruption as shown by propidium iodide (PI) positive staining and visible damage to cancer cell membranes under field emission scanning electron microscopy (FESEM). <em>In vivo</em> studies using a zebrafish model indicated favorable uptake and a lack of acute toxicity, depicting 80 % survival rate up to 4 μM of tested peptide concentration. Interestingly, the truncated variants of Ltc2a retained their alpha helical structure and demonstrated preferential uptake in MDA-MB-231 cells over HEK293T cells. These findings highlight the therapeutic potential of Ltc2a as selective anticancer peptide with minimal toxicity, paving the way for further preclinical development.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 7","pages":"Article 184442"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880266","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}

引用次数: 0