Biochimica et biophysica acta. Biomembranes最新文献_第4页

Differential insertion of arginine in saturated and unsaturated lipid vesicles 精氨酸在饱和和不饱和脂质囊泡中的不同插入。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-12-18 DOI: 10.1016/j.bbamem.2024.184405

Hugo A. Perez, María A. Brandan, Aníbal Disalvo, María de los A. Frías

{"title":"Differential insertion of arginine in saturated and unsaturated lipid vesicles","authors":"Hugo A. Perez, María A. Brandan, Aníbal Disalvo, María de los A. Frías","doi":"10.1016/j.bbamem.2024.184405","DOIUrl":"10.1016/j.bbamem.2024.184405","url":null,"abstract":"<div><div>In this work, the effects of L- Arginine (L-Arg) insertion on saturated and unsaturated lipid membranes were assessed by fluorescence spectroscopy, dynamic light scattering (DLS) and monolayer measurements. The studied systems were composed by DPPC, 16:0 DietherPC, 16:1 Δ9-CisPC, DPPC:Chol, 16:1 Δ9-CisPC:Chol, and 16:1 Δ9-CisPC:DPPC in the presence of increasing concentrations of L-Arg.</div><div>The information obtained using fluorescence spectral Laurdan properties indicates that L- Arg produces a decrease in the polarizability of saturated lipids congruent with the increase in vesicle size and area per lipid. However, in unsaturated lipids, the polarizability increases without significant changes in size and area per lipid denoting a different mechanism of insertion. The two opposite effects can be modulated by the saturated and unsaturated ratio and are independent of carbonyl groups. This modulation is damped by cholesterol. The differences in the L-Arg insertion can be explained considering that in the presence of the double bonds, L-Arg decreases the organized water in the lipid matrix without expanding the bilayer. Instead, in saturated lipid membranes, L-Arg inserts into the acyl chains dragging water and expanding the membrane area.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 3","pages":"Article 184405"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871178","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

Nanodomains enriched in arachidonic acid promote P2Y12 receptor oligomerization in the platelet plasma membrane 富含花生四烯酸的纳米域可促进血小板质膜中 P2Y12 受体的寡聚化。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-16 DOI: 10.1016/j.bbamem.2024.184402

Florentin Allemand , Semen Yesylevskyy , Jennifer Lagoutte-Renosi , Siamak Davani , Christophe Ramseyer

{"title":"Nanodomains enriched in arachidonic acid promote P2Y12 receptor oligomerization in the platelet plasma membrane","authors":"Florentin Allemand , Semen Yesylevskyy , Jennifer Lagoutte-Renosi , Siamak Davani , Christophe Ramseyer","doi":"10.1016/j.bbamem.2024.184402","DOIUrl":"10.1016/j.bbamem.2024.184402","url":null,"abstract":"<div><div>P2Y12 receptors on the platelet plasma membrane are targeted by several antiplatelets drugs. Although oligomerization and functioning of P2Y12 receptors depend on the membrane environment, little is known about their preferred membrane localization and the role of surrounding lipid composition, especially the arachidonic acids (ARA), which are abundant in platelets. Coarse-grained molecular dynamics simulations of platelet plasma membrane based on the lipidomics data were used to investigate the P2Y12 lipid environment and the involvement of ARA in its oligomerization in platelet plasma membranes. The platelet plasma membrane contains two types of lipids nanodomains: ordered, enriched in SM and cholesterol, and disordered, enriched in ARA-containing lipids. P2Y12 receptors prefer to localize in these ARA-rich domains and induce the sorting of the ARA-containing lipids in their vicinity. This ARA-rich environment promotes the oligomerization of P2Y12 receptors and stabilizes the protein-protein interfaces of oligomers. As summary, oligomerization of P2Y12 receptors is promoted in ARA-rich nano-domains of the platelet plasma membrane.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184402"},"PeriodicalIF":2.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667214","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

Successful strategies for expression and purification of ABC transporters 表达和纯化 ABC 转运体的成功策略。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-12 DOI: 10.1016/j.bbamem.2024.184401

Bea Berner , Georgia Daoutsali , Emilia Melén , Natália Remper , Emma Weszelovszká , Alice Rothnie , Kristina Hedfalk

{"title":"Successful strategies for expression and purification of ABC transporters","authors":"Bea Berner , Georgia Daoutsali , Emilia Melén , Natália Remper , Emma Weszelovszká , Alice Rothnie , Kristina Hedfalk","doi":"10.1016/j.bbamem.2024.184401","DOIUrl":"10.1016/j.bbamem.2024.184401","url":null,"abstract":"<div><div>ATP-binding cassette (ABC) transporters are proteins responsible for active transport of various compounds, from small ions to macromolecules, across membranes. Proteins from this superfamily also pump drugs out of the cell resulting in multidrug resistance. Based on the cellular functions of ABC-transporters they are commonly associated with diseases like cancer and cystic fibrosis. To understand the molecular mechanism of this critical family of integral membrane proteins, structural characterization is a powerful tool which in turn requires successful recombinant production of stable and functional protein in good yields. In this review we have used high resolution structures of ABC transporters as a measure of successful protein production and summarized strategies for prokaryotic and eukaryotic proteins, respectively. In general, <em>Escherichia coli</em> is the most frequently used host for production of prokaryotic ABC transporters while human embryonic kidney 293 (HEK293) cells are the preferred host system for eukaryotic proteins. Independent of origin, at least two-steps of purification were required after solubilization in the most used detergent DDM. The purification tag was frequently cleaved off before structural characterization using cryogenic electron microscopy, or crystallization and X-ray analysis for prokaryotic proteins.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 2","pages":"Article 184401"},"PeriodicalIF":2.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614113","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}

引用次数: 0

Bacterial flotillins as destabilizers of phospholipid membranes 作为磷脂膜脱稳剂的细菌絮凝物。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-08 DOI: 10.1016/j.bbamem.2024.184399

Ana Álvarez-Mena , Estelle Morvan , Denis Martinez , Melanie Berbon , Abigail Savietto Scholz , Axelle Grélard , Sarah Turpin , Erick J. Dufourc , Marc Bramkamp , Birgit Habenstein

{"title":"Bacterial flotillins as destabilizers of phospholipid membranes","authors":"Ana Álvarez-Mena , Estelle Morvan , Denis Martinez , Melanie Berbon , Abigail Savietto Scholz , Axelle Grélard , Sarah Turpin , Erick J. Dufourc , Marc Bramkamp , Birgit Habenstein","doi":"10.1016/j.bbamem.2024.184399","DOIUrl":"10.1016/j.bbamem.2024.184399","url":null,"abstract":"<div><div>From archaea to mammals evolutionary conserved flotillins are scaffolding proteins, recognized for their nandomain-segregating activity. Flotillins form basket-like oligomeric architectures on the membrane, based on a conserved secondary structure composition of the monomeric subunits: a membrane-targeting region, an SPFH domain and a coiled-coil “flotillin” domain. In <em>B. subtilis</em>, the two flotillins FloT and FloA are present, localizing mainly in distinct nanodomains and executing multiple cellular functions. We here use deuterium and phosphorus solid-state NMR to monitor the effect of the different flotillins FloT and FloA and their structural components on model membranes. We find a clear disordering effect of FloT and FloA on the membranes reaching the carbon positions in the centre of the membrane. This effect is imposed by the hydrophobic region and the adjacent SPFH domain and, surprisingly, further supported by the membrane-distant flotillin domain. Biological implications of this disordering action are discussed.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184399"},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614074","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}

引用次数: 0

Membrane fusion by dengue virus: The first step 登革热病毒的膜融合：第一步

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-08 DOI: 10.1016/j.bbamem.2024.184400

José Villalaín

{"title":"Membrane fusion by dengue virus: The first step","authors":"José Villalaín","doi":"10.1016/j.bbamem.2024.184400","DOIUrl":"10.1016/j.bbamem.2024.184400","url":null,"abstract":"<div><div>Flaviviruses include important human pathogens such as Dengue, Zika, West Nile, Yellow fever, Japanese encephalitis, and Tick-borne encephalitis viruses as well as some emerging viruses that affect millions of people worldwide. They fuse their membrane with the late endosomal one in a pH-dependent way and therefore the merging of the membranes is one of the main goals for obtaining new antivirals. The envelope E protein, a membrane fusion protein, is accountable for fusion and encompasses different domains involved in the fusion mechanism, including the fusion peptide segment. In this work we have used molecular dynamics to study the interaction of the distal end of domain II of the DENV envelope E protein with a membrane like the late endosomal membrane in order to observe the initiation of membrane fusion carried out by a number of trimers of the DENV envelope E protein interacting with a complex biomembrane and demonstrate its feasibility. Our results demonstrate the likelihood of membrane disorganization and pore formation by trimer complex organization, the amino acids responsible for such condition and the secondary structure arrangements needed for such fundamental process. At the same time, we define new targets of the envelope E protein sequence which could permit designing potent antiviral bioactive molecules.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184400"},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614096","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}

引用次数: 0

Antimicrobial and antibiofilm potential of α-MSH derived cationic and hydrophobic peptides against Escherichia coli: Mechanistic insight through peptide-lipopolysaccharide interactions α-MSH衍生的阳离子肽和疏水肽对大肠杆菌的抗菌和抗生物膜潜力：通过肽与脂多糖相互作用的机理研究。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-07 DOI: 10.1016/j.bbamem.2024.184398

Priya Patel , Swaleeha Jaan Abdullah , Kanchan Tiwari , Surajit Bhattacharjya , Kasturi Mukhopadhyay

{"title":"Antimicrobial and antibiofilm potential of α-MSH derived cationic and hydrophobic peptides against Escherichia coli: Mechanistic insight through peptide-lipopolysaccharide interactions","authors":"Priya Patel , Swaleeha Jaan Abdullah , Kanchan Tiwari , Surajit Bhattacharjya , Kasturi Mukhopadhyay","doi":"10.1016/j.bbamem.2024.184398","DOIUrl":"10.1016/j.bbamem.2024.184398","url":null,"abstract":"<div><div>The prevalence of infections caused by various Gram-negative pathogens specifically <em>Escherichia coli</em> continuously poses a significant challenge in health care as well as community settings owing to their ability to form biofilm and escalating tolerance towards available antibiotics. While most treatment regimes are targeted at eliminating the <em>E. coli</em> cells, the pathogenicity factors called endotoxin (lipopolysaccharides), associated with the sepsis initiation and the leading cause of death in intensive care units globally, are often ignored. In this study, the potency of alpha-melanocyte stimulating hormone based-peptides, particularly Ana-9 and Ana-10 against <em>E. coli</em> was investigated through microbiological, biophysical, and microscopic assays. Both Ana-9 and Ana-10 demonstrated enhanced activity against planktonic <em>E. coli</em> cells, and retained their activity against biofilm, which was supported by confocal microscopy. From the mechanistic perspective, spectroscopic studies indicated that the binding of peptides with LPS led to structural alteration of peptides due to their insertion into the hydrophobic environment of LPS. The electrostatic interaction of the peptide with LPS leads to outer membrane disorganization, allowing the peptide to access the inner membrane, depolarize it and ultimately inhibit the bacterial cells within the biofilm. These observations were further confirmed by atomic force and scanning electron microscopy. Thus, this study deepens our understanding of the structural characteristics of peptides attached to LPS, which could lead to the gradual improvement in developing more potent, broad-spectrum endotoxin neutralizers.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184398"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614066","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

Growth of Staphylococcus aureus in the presence of oleic acid shifts the glycolipid fatty acid profile and increases resistance to antimicrobial peptides 金黄色葡萄球菌在油酸存在下的生长会改变糖脂脂肪酸谱，并增加对抗菌肽的耐药性。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-11-03 DOI: 10.1016/j.bbamem.2024.184395

Djuro Raskovic , Gloria Alvarado , Kelly M. Hines , Libin Xu , Craig Gatto , Brian J. Wilkinson , Antje Pokorny

{"title":"Growth of Staphylococcus aureus in the presence of oleic acid shifts the glycolipid fatty acid profile and increases resistance to antimicrobial peptides","authors":"Djuro Raskovic , Gloria Alvarado , Kelly M. Hines , Libin Xu , Craig Gatto , Brian J. Wilkinson , Antje Pokorny","doi":"10.1016/j.bbamem.2024.184395","DOIUrl":"10.1016/j.bbamem.2024.184395","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> readily adapts to various environments and quickly develops antibiotic resistance, which has led to an increase in multidrug-resistant infections. Hence, <em>S. aureus</em> presents a significant global health issue and its adaptations to the host environment are crucial for understanding pathogenesis and antibiotic susceptibility. When <em>S. aureus</em> is grown conventionally, its membrane lipids contain a mix of branched-chain and straight-chain saturated fatty acids. However, when unsaturated fatty acids are present in the growth medium, they become a major part of the total fatty acid composition. This study explores the biophysical effects of incorporating straight-chain unsaturated fatty acids into <em>S. aureus</em> membrane lipids. Membrane preparations from cultures supplemented with oleic acid showed more complex differential scanning calorimetry scans than those grown in tryptic soy broth alone. When grown in the presence of oleic acid, the cultures exhibited a transition significantly above the growth temperature, attributed to the presence of glycolipids with long-chain fatty acids causing acyl chain packing frustration within the bilayer. Functional aspects of the membrane were assessed by studying the kinetics of dye release from unilamellar vesicles induced by the antimicrobial peptide mastoparan X. Dye release was slower from liposomes prepared from cells grown in oleic acid-supplemented cultures, suggesting that changes in membrane lipid composition and biophysics protect the cell membrane against peptide-induced lysis. These findings underscore the intricate relationship between the growth environment, membrane lipid composition, and the physical properties of the bacterial membrane, which should be considered when developing new strategies against <em>S. aureus</em> infections.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184395"},"PeriodicalIF":2.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582032","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

Voltage- and Ca2+-inducible PLC activity for analyzing PI(4,5)P2 sensitivity of ion channels in Xenopus oocytes 电压和 Ca2+ 诱导的 PLC 活性，用于分析爪蟾卵母细胞中离子通道对 PI(4,5)P2 的敏感性。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-10-30 DOI: 10.1016/j.bbamem.2024.184396

Takafumi Kawai , Natsuki Mizutani , Yasushi Okamura

{"title":"Voltage- and Ca2+-inducible PLC activity for analyzing PI(4,5)P2 sensitivity of ion channels in Xenopus oocytes","authors":"Takafumi Kawai , Natsuki Mizutani , Yasushi Okamura","doi":"10.1016/j.bbamem.2024.184396","DOIUrl":"10.1016/j.bbamem.2024.184396","url":null,"abstract":"<div><div>Phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) is a key membrane lipid regulating various ion channel activities. Currently, several molecular tools are used to modulate PIP<sub>2</sub> levels, each of which has distinct advantages and drawbacks. In this study, we proposed a novel methodology using heterologous <em>Xenopus</em> oocytes to precisely manipulate PIP<sub>2</sub> levels using phospholipase C (PLC)-ζ, which hydrolyzes PIP<sub>2</sub>. <em>Xenopus</em> oocytes injected with PLCζ exhibited notable hyperpolarization-induced Ca<sup>2+</sup> influx driven by the increased driving force of Ca<sup>2+</sup>. High Ca<sup>2+</sup> sensitivity of PLCζ facilitated hyperpolarization-induced PLC activity in <em>Xenopus</em> oocytes that was voltage- and Ca<sup>2+</sup>-dependent. This study demonstrated the regulatory capacity of PLCζ in modulating PIP<sub>2</sub>-sensitive ion channels, such as the KCNQ2/3 and GIRK channels, in a voltage- and Ca<sup>2+</sup>-dependent manner. Moreover, activation pathway of PLCζ only requires a two-electrode voltage clamp setup, making it a convenient molecular tool to manipulate PIP<sub>2</sub> levels in combination with a voltage-sensing phosphatase (VSP). PLCζ has distinct characteristics and advantages compared to VSP: (1) Hyperpolarization, but not depolarization, reduced the PIP<sub>2</sub> levels, (2) PIP<sub>2</sub> levels were decreased without any increase in phosphatidylinositol 4-monophosphate (PIP) levels, and (3) PIP<sub>2</sub> levels were reduced by Ca<sup>2+</sup> administration. Therefore, PLCζ effectively supports understanding how PIP<sub>2</sub> regulates ion channels, alongside VSP. Overall, this study highlights the unique characteristics of PLCζ and its distinct advantages in analyzing ion channel regulation by PIP<sub>2</sub> and the PLC pathway in <em>Xenopus</em> oocytes.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184396"},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557053","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}

引用次数: 0

Lipid bilayer permeabilities and antibiotic effects of tetramethylguanidinium and choline fatty acid ionic liquids 四甲基胍和胆碱脂肪酸离子液体的脂质双分子层渗透性和抗生素效应。

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-10-22 DOI: 10.1016/j.bbamem.2024.184393

Achismita Dutta , Brandon Burrell , Esha Prajapati , Sierra Cottle , Hailey Y. Maurer , Matthew J. Urban , Samuel R. Pennock , Arwa M. Muhamed , Janiyah Harris , Yesenia Flores , Lauren Staman , Benjamin R. Carone , Gregory A. Caputo , Timothy D. Vaden

{"title":"Lipid bilayer permeabilities and antibiotic effects of tetramethylguanidinium and choline fatty acid ionic liquids","authors":"Achismita Dutta , Brandon Burrell , Esha Prajapati , Sierra Cottle , Hailey Y. Maurer , Matthew J. Urban , Samuel R. Pennock , Arwa M. Muhamed , Janiyah Harris , Yesenia Flores , Lauren Staman , Benjamin R. Carone , Gregory A. Caputo , Timothy D. Vaden","doi":"10.1016/j.bbamem.2024.184393","DOIUrl":"10.1016/j.bbamem.2024.184393","url":null,"abstract":"<div><div>Ionic liquids (ILs) have been studied as potential components in antibiotic formulations based on their abilities to permeabilize and penetrate lipid bilayer, which correlate with their antibacterial effects. Fatty acid-based ILs (FAILs), in which the anion is a long-chain fatty acid, can permeabilize lipid membranes and have been used in biomedical applications since they have low human cell cytotoxicity. In this work we investigated the abilities of several different FAILs to permeabilize lipid bilayers and how that permeabilization correlates with antibacterial activity, cell membrane permeability, and cytotoxicity. The FAILs consisted of the cations tetramethylguanidinium (TMG) or choline combined with octanoate or decanoate. These FAILs were tested on model bilayer vesicles with three different lipid compositions for membrane permeabilization using a leakage assay. They were then tested for antibiotic and membrane permeabilization on bacterial and mammalian cells. The results show that while the octanoate-based FAILs do not form micelles and have low activities on vesicles and biological cells, the decanoate-based FAILs can permeabilize bilayers and have biological activities that correlate with the model vesicle results. The ILs with both cation and fatty-acid anion have strong activities while the decanoate alone has only minimal permeabilization and antibiotic activity. Membrane permeabilization occurs at FAIL concentrations below their CMC values which suggests that their mechanism of action may not involve micelle formation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184393"},"PeriodicalIF":2.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493945","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

TNF receptors: Structure-function relationships and therapeutic targeting strategies TNF 受体：结构-功能关系和靶向治疗策略

IF 2.8 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2024-10-22 DOI: 10.1016/j.bbamem.2024.184394

Chih Hung Lo

{"title":"TNF receptors: Structure-function relationships and therapeutic targeting strategies","authors":"Chih Hung Lo","doi":"10.1016/j.bbamem.2024.184394","DOIUrl":"10.1016/j.bbamem.2024.184394","url":null,"abstract":"<div><div>Tumor necrosis factor receptors (TNFR1 and TNFR2) play key roles in mediating inflammatory response and cell death signaling, which are associated with autoimmune disorders, neurodegenerative diseases, and cancers. The structure-function relationships of TNF receptors and their ligands determine the activation or inhibition of downstream signaling pathways. Available crystal structures have provided critical insights into the therapeutic targeting strategies of TNF receptors and their signaling networks. In this review, we discuss the potential of targeting receptor-ligand and receptor-receptor interactions in a competitive manner as well as perturbing receptor conformational dynamics through an allosteric mechanism to modulate TNF receptor signaling. We propose that conformational states of TNF receptors can act as a molecular switch in determining their functions and are important therapeutic targets. The knowledge of the structure-function relationships of TNF receptors can be applied to translational high-throughput drug screening and design of novel receptor-specific modulators with enhanced pharmacological properties.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 1","pages":"Article 184394"},"PeriodicalIF":2.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493944","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