Biochimica et biophysica acta. Biomembranes最新文献

{"title":"Elucidating the interactions of endocannabinoid-like neurotransmitters, N-acyltaurines and bovine serum albumin: Spectroscopic and computational approaches","authors":"Martin Luther John ,&nbsp;Sivaramakrishna Akella ,&nbsp;Ravi Kanth Kamlekar","doi":"10.1016/j.bbamem.2025.184421","DOIUrl":"10.1016/j.bbamem.2025.184421","url":null,"abstract":"<div><div><em>N</em>-Acyltaurines (NATs) are endogenous neurotransmitters, structurally similar to endocannabinoids, and have anti-inflammatory and anti-proliferative effects. In response to NATs, TRP channels, TRPV1, TRPV4 and the peptide hormone, GLP-1 are activated. Serum albumin proteins act as transporters for a variety of substances in blood plasma (i.e., hormones, fatty acids, bilirubin, ions, and medications). Due to the structural closeness of Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA), a study into NAT-BSA interactions is crucial. To study interactions of NATs (<em>n</em> = 10–18) with BSA, spectroscopic and computational techniques were used. From the steady-state fluorescence measurements, observed binding constants are in the range of 1.57 × 10⁵ M⁻¹ to 2.85 × 10⁵ M⁻¹. Due to the binding of NATs, the fluorescence of BSA is quenched (∼24.77 %). The negative enthalpy and entropy change and Gibbs free energy values, obtained from van't Hoff plot indicate that the interactions between NATs and BSA are spontaneous and primarily driven by hydrogen bonding. Competitive site-binding assays with warfarin and ibuprofen show that NATs bind to both the drug-binding sites in BSA concurrently. The CD spectroscopic and FT-IR analysis indicates relatively marginal changes in the secondary structure of BSA. Molecular docking analyses are done to identify binding locations and molecular-level interactions. The negative free energy values indicate that NATs have a positive binding relationship with BSA. These findings are congruent with the findings of site-binding studies, which reveal that NATs have a higher proclivity for interacting with sites I and II at the same time.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184421"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844050","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}

{"title":"Effect of osmolytes on the conformational stability of Aβ(25–35): A circular dichroism analysis","authors":"Angelo Santoro ,&nbsp;Michela Buonocore ,&nbsp;Anna Maria D'Ursi","doi":"10.1016/j.bbamem.2025.184420","DOIUrl":"10.1016/j.bbamem.2025.184420","url":null,"abstract":"<div><div>Alzheimer's (AD) is a neurodegenerative disease characterized by the onset and progression of mental decline. AD aetiopathogenesis is still questioned; however, according to one of the most accredited hypotheses, the accumulation of amyloid plaques formed by aggregated Aβ peptides is the primary cause of neuronal function loss. Accordingly, hundreds of molecules have been screened for their possible action to prevent or destroy amyloid aggregates. Following this track, osmolytes, naturally occurring small molecules produced by several organisms in response to external stressors, were recently evaluated as modulators of Aβ aggregation. In this study, we examined the conformational stability of Aβ(25–35) when exposed to the osmolytes acetylcholine (ACh), succinylcholine (SCh), and betaine (Bet). Aβ(25–35) is the shortest fragment known for replicating the aggregation process seen in Aβ peptides. By collecting circular dichroism (CD) spectra in water and different membrane-mimicking systems, we investigated the potential of the mentioned osmolytes to stabilize the soluble conformations of Aβ(25–35) and preserve them from denaturing conditions. Our data suggest that Bet is a promising small molecule that can safeguard the soluble form of Aβ peptide and is effective in counteracting environmental conditions by favoring the amyloid aggregation associated with pathology progression.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184420"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-chain cationic gemini surfactants as drug retention adjuvant on liposomes. A methodological approach with atorvastatin","authors":"Yago Radziunas-Salinas ,&nbsp;Vicente Domínguez-Arca ,&nbsp;Alberto Pardo ,&nbsp;Adriana Cambón ,&nbsp;Pablo Taboada ,&nbsp;Gerardo Prieto","doi":"10.1016/j.bbamem.2025.184419","DOIUrl":"10.1016/j.bbamem.2025.184419","url":null,"abstract":"<div><div>This study delves into the development and characterization of dipalmitoyl phosphatidylcholine (DPPC) liposomes incorporated with gemini surfactant (tetradecamethylene-1,14 bis(dimethyl tetradecyl ammonium bromide); 14-14-14) and atorvastatin, aimed at enhancing drug delivery efficiency for cardiovascular diseases. The integration of gemini surfactants into liposomes is investigated for its potential to improve atorvastatin encapsulation and retention, addressing the drug's poor water solubility and the limitations of conventional liposomal systems. Through a combination of dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular dynamics (MD) simulations, the study reveals that the presence of gemini surfactants significantly reduces liposome size and polydispersity, indicative of a more uniform and potentially unilamellar structure. DSC analysis highlights a decrease in transition temperatures and an alteration in transition symmetry, suggesting enhanced stability and a favourable drug release profile at physiological temperatures. MD simulations provide insight into the internalization mechanism of gemini surfactants and atorvastatin within the liposomal bilayer, demonstrating their mutual incorporation facilitated by polar interactions. Spectrophotometry-based retention studies further confirmed that liposomes containing gemini surfactants exhibit superior atorvastatin retention capabilities, nearly doubling the encapsulation efficiency compared to conventional liposomes. This research highlights the promising role of gemini surfactant-incorporated liposomes as an efficient drug delivery platform for cardiovascular therapeutics, offering insights into the molecular interactions and structural dynamics underlying their enhanced performance.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184419"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787602","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}

{"title":"Replacement of phenyl substituents at phosphorus by hexyl ones in 2-(2-hydroxyaryl)vinylphosphonium salts can tune the nature of the induced proton transport through lipid membranes","authors":"Tatyana I. Rokitskaya ,&nbsp;Ljudmila S. Khailova ,&nbsp;Anna G. Strelnik ,&nbsp;Elena A. Kotova ,&nbsp;Vladimir F. Mironov ,&nbsp;Dmitry A. Tatarinov ,&nbsp;Yuri N. Antonenko","doi":"10.1016/j.bbamem.2025.184417","DOIUrl":"10.1016/j.bbamem.2025.184417","url":null,"abstract":"<div><div>2-(2-hydroxyaryl)vinylphosphonium salts are zwitterionic protonophores previously shown to induce proton transport across lipid membranes via cyclic deprotonation and protonation of the hydroxyl group. Here, we examine the impact of the kind of substituents at phosphorus on the protonophoric activity of these compounds. In particular, replacement of all the three phenyl groups at the phosphorus atom of the 2-(2-hydroxyaryl)vinyl(triphenyl)phosphonium salt (<strong>2HVPPh</strong>_{<strong>3</strong>}) by hexyl chains (<strong>2HVPHex</strong>_{<strong>3</strong>}) led to a tremendous increase in electric current induced by the phosphonium salt across planar bilayer lipid membranes (BLM). Remarkably, the BLM conductance quadratically increased with increasing <strong>2HVPHex</strong>_{<strong>3</strong>} concentration, whereas a linear concentration dependence of the BLM current was observed for <strong>2HVPPh</strong>_{<strong>3</strong>}, <strong>2HVPHexPh</strong>_{<strong>2</strong>} ((hexyl)diphenyl) and <strong>2HVPHex</strong>_{<strong>2</strong>}<strong>Ph</strong> ((dihexyl)phenyl), i.e., in the presence of at least one phenyl substituent at the phosphorus atom. Proton selectivity of the <strong>2HVPHex</strong>_{<strong>3</strong>}-induced electric current was close to perfect in membranes formed of diphytanylphosphatidylcholine with the decreased dipole potential, but rather low in membranes formed of the usual synthetic lipid – diphytanoylphosphatidylcholine. We hypothesize that the proton transport across BLM is carried out by <strong>2HVPHex</strong>_{<strong>3</strong>} dimers. By contrast, the uncoupling activity of <strong>2HVPHex</strong>_{<strong>3</strong>} in isolated rat liver mitochondria was observed at similar concentrations, as found for the compounds with phenyl substituents, thereby indicating that dimers do not play a key role in the uncoupling process. At the same time, the rate of <strong>2HVPHex</strong>_{<strong>3</strong>}-induced mitochondrial swelling under the deenergized conditions in potassium acetate medium, reflecting the protonophoric activity of the compound in mitochondria, significantly exceeded that for other compounds.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 3","pages":"Article 184417"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453902","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}

{"title":"Corrigendum to \"Structural analysis of the NK-lysin-derived peptide NK-2 upon interaction with bacterial membrane mimetics consisting of phosphatidylethanolamine and phosphatidylglycerol\" [BBA - Biomembr. 1866 (2024) 184267].","authors":"Jörg Andrä, Christopher Aisenbrey, U S Sudheendra, Marc Prudhon, Gerald Brezesinski, Evgeniy S Salnikov, Claudia Zschech, Regine Willumeit-Römer, Matthias Leippe, Thomas Gutsmann, Burkhard Bechinger","doi":"10.1016/j.bbamem.2025.184416","DOIUrl":"10.1016/j.bbamem.2025.184416","url":null,"abstract":"","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184416"},"PeriodicalIF":2.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381577","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}

{"title":"Lipopolysaccharide supramolecular organization regulates the activation of coagulation factor XII","authors":"André L. Lira ,&nbsp;Ting Liu ,&nbsp;Joseph E. Aslan ,&nbsp;Cristina Puy ,&nbsp;Owen J.T. McCarty","doi":"10.1016/j.bbamem.2025.184415","DOIUrl":"10.1016/j.bbamem.2025.184415","url":null,"abstract":"<div><div>Lipopolysaccharides (LPS) are key bacterial membrane components that activate coagulation factor XII (FXII), establishing a critical link between bacterial infections, blood coagulation, and inflammation. This study investigates how the supramolecular organization of LPS—monomers, micelles, and bilayers—affects FXII activation. We demonstrate that LPS micelles uniquely activate FXII to its enzymatic form (FXIIa), while monomeric LPS modulates FXIIa activity without direct activation, and bilayer-form LPS does not induce FXII activation. The addition of calcium ions (Ca²⁺) promoted the formation of bilayers by binding to the negatively charged phosphate groups of LPS, reducing electrostatic repulsion and stabilizing LPS aggregates, potentially leading to a shift in their net charge. These findings highlight the pivotal role of LPS supramolecular structure in modulating FXII activity, providing mechanistic insights into the interplay between bacterial components and the coagulation cascade.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 3","pages":"Article 184415"},"PeriodicalIF":2.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349958","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}

{"title":"Lock and key: Quest to find the most compatible membrane mimetic for studying membrane proteins in native environment","authors":"Rahul Yadav ,&nbsp;Debarghya Pratim Gupta ,&nbsp;Chandan Singh","doi":"10.1016/j.bbamem.2025.184414","DOIUrl":"10.1016/j.bbamem.2025.184414","url":null,"abstract":"<div><div>Membrane proteins play crucial roles in cellular signal transduction, molecule transport, host-pathogen interactions, and metabolic processes. However, mutations, changes in membrane properties, and environmental factors can lead to loss of protein function. This results in impaired ligand binding and misfolded structures that prevent proteins from adopting their native conformation. Many membrane proteins are also therapeutic targets in various diseases, where drugs can either restore or inhibit their specific functions. Understanding membrane protein structure and function is vital for advancing cell biology and physiology. Experimental studies often involve extracting proteins from their native environments and reconstituting them in membrane mimetics like detergents, bicelles, amphipols, nanodiscs, and liposomes. These mimetics replicate aspects of native membranes, aiding in the study of protein behavior outside living cells. Scientists continuously explore new, more native-like membrane mimetics to improve experimental accuracy. This dynamic field involves evaluating the advantages and disadvantages of different mimetics and optimizing the reconstitution process to better mimic natural conditions.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 3","pages":"Article 184414"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363538","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}

{"title":"The effect of oxidative stress on the adenosine A2A receptor activity and signalling","authors":"Idoia Company-Marín ,&nbsp;Joseph Gunner ,&nbsp;David Poyner ,&nbsp;John Simms ,&nbsp;Andrew R. Pitt ,&nbsp;Corinne M. Spickett","doi":"10.1016/j.bbamem.2025.184412","DOIUrl":"10.1016/j.bbamem.2025.184412","url":null,"abstract":"<div><div>The adenosine A_2A receptor (A_2AR) is a G-protein coupled receptor that has important anti-inflammatory effects in response to some agonists and consequently is considered a therapeutic target. Its activity is affected by local membrane lipid environment and presence of certain phospholipid classes, so studies should be conducted using extraction methods such as styrene maleic acid <em>co</em>-polymers (SMA) that retain the local lipids. Currently, little is known about the effect of oxidative stress, which may arise from inflammation, on the A_2AR. Therefore, it was over-expressed in <em>Pichia pastoris</em>, SMA was used to extract the A_2AR from cell membranes and its response to ligands was tested in the presence or absence of the radical initiator AAPH or reactive aldehyde acrolein. SMA-extracted A_2AR was able to undergo conformational changes, measured by tryptophan fluorescence, in response to its ligands but oxidative treatments had no effect on the structural changes. Similarly, the treatments did not affect temperature-dependent protein unfolding. In contrast, in HEK293 cells expressing the A_2AR, oxidative treatments increased cAMP levels in response to the agonist NECA but had no effect on direct activation of adenylate cyclase. Thus, oxidative stress may be a homeostatic mechanism that abrogates inflammation via the A_2AR signalling pathway.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 3","pages":"Article 184412"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning expression of GPCRs for the secretory pathway in the baculovirus-insect cell expression system","authors":"Jakob Aastrup Jørgensen","doi":"10.1016/j.bbamem.2024.184397","DOIUrl":"10.1016/j.bbamem.2024.184397","url":null,"abstract":"<div><div>The overexpression of G-protein-coupled receptors (GPCRs) remains one of the biggest hurdles for structural studies of these proteins. To date, the most usually applied system for this task is the insect cell/baculovirus expression system. A drawback of this system, however, is the accumulation of protein that is resistant to solubilization with the commonly used mild detergent DoDecylMaltoside (DDM). In addition, poor surface expression is often observed. In this study, it is shown how an earlier AcMNPV 39K promoter, can express receptors that are found primarily on the cell membrane, as revealed by confocal microscopy, and the protein can be solubilized to a higher degree by DDM in a less aggregation-prone form, as monitored by fluorescence size-exclusion chromatography. In addition, a strong effect on the yield was observed when the AcMNPV gp67 signal sequence was used. The documentation of the 39K promoter as an improvement over the frequently used polyhedrin promoter, along with the effect of the gp67 signal sequence are important steps toward ultimately improving the expression in terms of total functional yield, while also shedding light on the nature of the process of overproduction of membrane proteins, in particular, GPCRs.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 2","pages":"Article 184397"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543407","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}

{"title":"Characterization of intact FeoB in a lipid bilayer using styrene-maleic acid (SMA) copolymers","authors":"Mark Lee,&nbsp;Candice M. Armstrong,&nbsp;Aaron T. Smith","doi":"10.1016/j.bbamem.2024.184404","DOIUrl":"10.1016/j.bbamem.2024.184404","url":null,"abstract":"<div><div>The acquisition of ferrous iron (Fe²⁺) is crucial for the survival of many pathogenic bacteria living within acidic and/or anoxic conditions such as <em>Vibrio cholerae</em>, the causative agent of the disease cholera. Bacterial pathogens utilize iron as a cofactor to drive essential metabolic processes, and the primary prokaryotic Fe²⁺ acquisition mechanism is the ferrous iron transport (Feo) system. In <em>V. cholerae</em>, the Feo system comprises two cytosolic proteins (FeoA, FeoC) and a complex, polytopic transmembrane protein (FeoB) that is regulated by an N-terminal soluble domain (NFeoB) with promiscuous NTPase activity. While the soluble components of the Feo system have been frequently studied, very few reports exist on the intact membrane protein FeoB. Moreover, FeoB has been characterize almost exclusively in detergent micelles that can cause protein misfolding, disrupt protein oligomerization, and even dramatically alter protein function. As many of these characteristics of FeoB remain unclear, there is a critical need to characterize FeoB in a more native-like lipid environment. To address this unmet need, we employ styrene-maleic acid (SMA) copolymers to isolate and to characterize <em>V. cholerae</em> FeoB (<em>Vc</em>FeoB) encapsulated by a styrene-maleic acid lipid particle (SMALP). In this work, we describe the development of a workflow for the expression and the purification of <em>Vc</em>FeoB in a SMALP. Leveraging mass photometry, we explore the oligomerization of FeoB in a lipid bilayer and show that the <em>Vc</em>FeoB-SMALP is mostly monomeric, consistent with our previous oligomerization observations <em>in surfo</em>. Finally, we characterize the NTPase activity of <em>Vc</em>FeoB in the SMALP and in a detergent (DDM), revealing higher NTPase activity in the presence of the lipid bilayer. When taken together, this report represents the first characterization of any FeoB in a native-like lipid bilayer and provides a viable approach for the future structural characterization of FeoB.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 2","pages":"Article 184404"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852335","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}