Journal of Membrane Biology最新文献

{"title":"Computational Insights on the Assembly of the Dengue Virus Membrane-Capsid-RNA Complex.","authors":"Dwaipayan Chaudhuri, Satyabrata Majumder, Joyeeta Datta, Kalyan Giri","doi":"10.1007/s00232-025-00337-4","DOIUrl":"10.1007/s00232-025-00337-4","url":null,"abstract":"<p><p>Dengue virus, an arbovirus from the genus Flavivirus in the family Flaviviridae, forms a nucleocapsid structure through interactions between its genome and multiple copies of the capsid protein. Experimental studies have confirmed the interaction between the viral capsid protein and lipid droplets, indicating a protein-lipid interaction. Cryo-EM studies show that in immature viruses, the nucleocapsid is located close to the viral membrane. This study uses multiple MD simulations to explore the orientation of the capsid protein relative to the lipid membrane, focusing on how the protein's hydrophobic pocket interacts with the membrane. We also investigated the interaction between the capsid protein and RNA, considering the effects of sequence length and identity. Finally, we construct a model of the lipid-protein-RNA complex, demonstrating that the capsid protein's hydrophobic pocket interacts with the membrane, while the positively charged H4 helix interacts with the negatively charged RNA. This research may identify crucial interactions for immature virus particle formation and provide insights for future therapeutic interventions.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"75-96"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Free Systems and Their Importance in the Study of Membrane Proteins.","authors":"Karen Stephania González-Ponce, Samuel Celaya-Herrera, María Fernanda Mendoza-Acosta, Luz Edith Casados-Vázquez","doi":"10.1007/s00232-024-00333-0","DOIUrl":"10.1007/s00232-024-00333-0","url":null,"abstract":"<p><p>The Cell-Free Protein Synthesis (CFPS) is an innovative technique used to produce various proteins. It has several advantages, including short expression times, no strain engineering is required, and toxic proteins such as membrane proteins can be produced. However, the most important advantage is that it eliminates the need for a living cell as a production system. Membrane proteins (MPs) are difficult to express in heterologous strains such as Escherichia coli. Modified strains must be used, and sometimes the strain produces them as inclusion bodies, which makes purification difficult. CFPS can avoid the problem of toxicity and, with the use of additives, allows the production of folded and functional membrane proteins. In this review, we focus on describing what cell-free systems are. We address the advantages and disadvantages of the different organisms that can be used to obtain cell extracts, including PURE systems, where the components are obtained recombinantly, and the methodologies that allow the synthesis of membrane proteins in cell-free systems, which, given their hydrophobic nature, require additives for their correct folding.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"15-28"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Swollen State in Cell Proliferation.","authors":"Behor Eleazar Cohen","doi":"10.1007/s00232-024-00328-x","DOIUrl":"10.1007/s00232-024-00328-x","url":null,"abstract":"<p><p>Cell swelling is known to be involved in various stages of the growth of plant cells and microorganisms but in mammalian cells how crucial a swollen state is for determining the fate of the cellular proliferation remains unclear. Recent evidence has increased our understanding of how the loss of the cell surface interactions with the extracellular matrix at early mitosis decreases the membrane tension triggering curvature changes in the plasma membrane and the activation of the sodium/hydrogen (Na +/H +) exchanger (NHE1) that drives osmotic swelling. Such a swollen state is temporary, but it is critical to alter essential membrane biophysical parameters that are required to activate Ca2 + channels and modulate the opening of K + channels involved in setting the membrane potential. A decreased membrane potential across the mitotic cell membrane enhances the clustering of Ras proteins involved in the Ca2 + and cytoskeleton-driven events that lead to cell rounding. Changes in the external mechanical and osmotic forces also have an impact on the lipid composition of the plasma membrane during mitosis.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic characterization and evaluation of oxidative stress effects of digitoxigenin derivatives on HeLa cells.","authors":"Jessica M M Valadares, Pedro Azalim-Neto, Xiaofan Liu, Nathallia Cavalcanti Carrozza, George A O'Doherty, Luis Eduardo M Quintas, Leandro A Barbosa","doi":"10.1007/s00232-024-00334-z","DOIUrl":"10.1007/s00232-024-00334-z","url":null,"abstract":"<p><p>Cancer is a leading cause of death worldwide and its treatment is hampered by the lack of specificity and side effects of current drugs. Cardiotonic steroids (CTS) interact with Na⁺/K⁺-ATPase (NKA) and induce antineoplastic effects, but their narrow therapeutic window is key limiting factor. The synthesis of digitoxigenin derivatives with glycosidic unit modifications is a promising approach to develop more selective and effective antitumor agents. This study aimed to compare the pharmacological properties as well as the cytotoxic effects of digitoxigenin-α-L-amiceto-pyranoside and digitoxigenin-α-L-rhamno-pyranoside and to evaluate the mechanism of these derivatives in oxidative conditions in HeLa cells. The rhamnose derivative increased the binding affinity and inhibitory effect of digitoxigenin by approximately 5-15 times, unlike the amicetose derivative. Despite this difference, both compounds similarly increased H₂O₂ levels, induced membrane lipid peroxidation, and reduced GSH levels and SOD activity at nanomolar concentrations. This study highlights the importance of the sugar moiety in CTS structure for NKA binding and demonstrates that a primary mechanism of cytotoxicity of digitoxigenin derivatives may involve cellular oxidative stress, underscoring their potential as therapeutic agents for cancer treatment.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"63-73"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Triterpenoids Betulin and Betulinic Acid on Pulmonary Surfactant Membranes.","authors":"Cisem Altunayar-Unsalan, Ozan Unsalan","doi":"10.1007/s00232-024-00329-w","DOIUrl":"10.1007/s00232-024-00329-w","url":null,"abstract":"<p><p>The purpose of this work is to examine how triterpenoids betulin (BE) and betulinic acid (BA) affect the thermotropic phase behaviour and bilayer packing in pulmonary surfactant membranes. Therefore, the interaction of these triterpenoids with dipalmitoylphosphatidylcholine (DPPC) bilayers is studied by differential scanning calorimetry (DSC), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM), and quantum chemical computations with density functional theory (DFT). From DSC data, the effects are more pronounced with BE compared to BA. At BE concentration of 20 mol%, the pretransition does not completely disappear and the lamellar phase transition broadens further. There are two indistinguishable peaks in the main phase transition, which may indicate the start of inhomogeneous mixing or phase separation in the gel phase. BA reduces the main transition temperature and almost completely eliminates the pretransition at concentrations of 1-10 mol%. Endotherms continue to have a symmetric, broad form that suggests perfect mixing. From ATR-FTIR data, both triterpenoids display the CH₂ antisymmetric stretching, C = O stretching, PO₂^- asymmetric stretching to higher wavenumber in DPPC system. These results indicate an increase in the lateral mobility and dehydration in the polar head group and glycerol-acyl chain interface of DPPC liposomes. From microscopic results, it is found that the addition of high concentration (20 mol%) of BE and BA into pure DPPC membranes, single and double planar layers are formed, and the size of the liposomes increases. According to computational studies, the O₁₃₁-H₂₀₆ OH group of BE and the P₂₄-O₂₆ head group of DPPC formed a hydrogen bonding of 1.805 Å between BE and DPPC in gas phase. This hydrogen bonding is observed between BA and DPPC via the P₂₄-O₂₆ head group of DPPC and the O₁₃₂-H₂₀₉ OH group of BA.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"47-61"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue Virus Fusion Peptide Promotes Hemifusion Formation by Disordering the Interfacial Region of the Membrane.","authors":"Smruti Mishra, Hirak Chakraborty","doi":"10.1007/s00232-025-00336-5","DOIUrl":"https://doi.org/10.1007/s00232-025-00336-5","url":null,"abstract":"<p><p>Membrane fusion is the first step in the infection process of the enveloped viruses. Enveloped viruses fuse either at the cell surface or enter the cell through endocytosis and transfer their internal genetic materials by fusing with the endosomal membrane at acidic pH. In this work, we have evaluated the effect of the Dengue virus fusion peptide (DENV FP) on the polyethylene glycol (PEG)-mediated lipid mixing of vesicles (hemifusion formation) at pH 5 and pH 7.4 with varying cholesterol concentrations. We have demonstrated that the DENV FP promotes hemifusion formation during the fusion of small unilamellar vesicles (SUVs) mainly at pH 5.0. Moreover, the fusion process demonstrates a strong correlation between fusogenicity and the amount of membrane cholesterol. We have further evaluated the partitioning ability of the peptide in three different membranes at pH 5.0 and pH 7.4. The fusogenic ability of the peptide at pH 5.0 is associated with the composition-dependent binding affinity of the peptide to the membrane. The depth-dependent fluorescence probes are used to evaluate membrane organization and dynamics utilizing steady-state and time-resolved fluorescence spectroscopic techniques. Our results show that the DENV FP promotes hemifusion formation by fluidizing the interfacial region of the membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hetero-Oligomeric Protein Pores for Single-Molecule Sensing.","authors":"Remya Satheesan, Asuma Janeena, Kozhinjampara R Mahendran","doi":"10.1007/s00232-024-00331-2","DOIUrl":"https://doi.org/10.1007/s00232-024-00331-2","url":null,"abstract":"<p><p>Protein nanopores are emerging as versatile single-molecule sensors with broad applications in DNA and protein sequencing. However, their narrow size restricts the range of detectable analytes, necessitating the development of advanced nanopores to broaden their applications in biotechnology. This review highlights a natural hetero-oligomeric porin, Nocardia farcinica porin AB (NfpAB), based on the Gram-positive mycolata, Nocardia farcinica. The pore comprises two subunits, NfpA and NfpB, that combine to form a stable structure with a unique pore geometry, asymmetrical shape, and charge distribution. Single-channel electrical recordings demonstrate that NfpAB forms stable, high-conductance channels suitable for sensing charged molecules, particularly cationic polypeptides and cyclic sugars. This pore offers advantages such as enhanced control over molecular interactions due to densely crowded charged residues, thus allowing the quantification of voltage-dependent translocation kinetics. Notably, NfpAB contains intrinsic cysteines in the pore lumen, providing an accessible site for thiol-based reactions and attachment of molecular adapters. We propose that such hetero-oligomeric pores will be effective for several applications in nanopore technology for biomolecular detection and sequencing.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of an Oomycete Nep1-like Cytolysin with Natural and Plant Cell-Mimicking Membranes.","authors":"Tina Snoj, Tjaša Lukan, Kristina Gruden, Gregor Anderluh","doi":"10.1007/s00232-024-00330-3","DOIUrl":"https://doi.org/10.1007/s00232-024-00330-3","url":null,"abstract":"<p><p>Plants are attacked by various pathogens that secrete a variety of effectors to damage host cells and facilitate infection. One of the largest and so far understudied microbial protein families of effectors is necrosis- and ethylene-inducing peptide-1-like proteins (NLPs), which are involved in important plant diseases. Many NLPs act as cytolytic toxins that cause cell death and tissue necrosis by disrupting the plant's plasma membrane. Their mechanism of action is unique and leads to the formation of small, transient membrane ruptures. Here, we capture the interaction of the cytotoxic model NLP from the oomycete Pythium aphanidermatum, NLP_Pya, with plant cell-mimicking membranes of giant unilamellar vesicles (GUVs) and tobacco protoplasts using confocal fluorescence microscopy. We show that the permeabilization of GUVs by NLP_Pya is concentration- and time-dependent, confirm the small size of the pores by observing the inability of NLP_Pya monomers to pass through them, image the morphological changes of GUVs at higher concentrations of NLP_Pya and confirm its oligomerization on the membrane of GUVs. In addition, NLP_Pya bound to plasma membranes of protoplasts, which showed varying responses. Our results provide new insights into the interaction of NLP_Pya with model lipid membranes containing plant-derived sphingolipids.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voltage Gated Ion Channels and Sleep.","authors":"Yan Zhang, Jiawen Wu, Yuxian Zheng, Yangkun Xu, Ziqi Yu, Yong Ping","doi":"10.1007/s00232-024-00325-0","DOIUrl":"10.1007/s00232-024-00325-0","url":null,"abstract":"<p><p>Ion channels are integral components of the nervous system, playing a pivotal role in shaping membrane potential, neuronal excitability, synaptic transmission and plasticity. Dysfunction in these channels, such as improper expression or localization, can lead to irregular neuronal excitability and synaptic communication, which may manifest as various behavioral abnormalities, including disrupted rest-activity cycles. Research has highlighted the significant impact of voltage gated ion channels on sleep parameters, influencing sleep latency, duration and waveforms. Furthermore, these ion channels have been implicated in the vulnerability to, and the pathogenesis of, several neurological and psychiatric disorders, including epilepsy, autism, schizophrenia, and Alzheimer's disease (AD). In this comprehensive review, we aim to provide a summary of the regulatory role of three predominant types of voltage-gated ion channels-calcium (Ca²⁺), sodium (Na⁺), and potassium (K⁺)-in sleep across species, from flies to mammals. We will also discuss the association of sleep disorders with various human diseases that may arise from the dysfunction of these ion channels, thereby underscoring the potential therapeutic benefits of targeting specific ion channel subtypes for sleep disturbance treatment.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"269-280"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postsynaptic Density Proteins and Their Role in the Trafficking of Group I Metabotropic Glutamate Receptors.","authors":"K Aruna, Subhajit Pal, Ankita Khanna, Samarjit Bhattacharyya","doi":"10.1007/s00232-024-00326-z","DOIUrl":"10.1007/s00232-024-00326-z","url":null,"abstract":"<p><p>Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system that regulates multiple different forms of synaptic plasticity, including learning and memory. Glutamate transduces its signal by activating ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Group I mGluRs belong to the G protein-coupled receptor (GPCR) family. Regulation of cell surface expression and trafficking of the glutamate receptors represents an important mechanism that assures proper transmission of information at the synapses. There is growing evidence implicating dysregulated glutamate receptor trafficking in the pathophysiology of several neuropsychiatric disorders. The postsynaptic density (PSD) region consists of many specialized proteins which are assembled beneath the postsynaptic membrane of dendritic spines. Many of these proteins interact with group I mGluRs and have essential roles in group I mGluR-mediated synaptic function and plasticity. This review provides up-to-date information on the molecular determinants regulating cell surface expression and trafficking of group I mGluRs and discusses the role of few of these PSD proteins in these processes. As substantial evidences link mGluR dysfunction and maladaptive functioning of many PSD proteins to the pathophysiology of various neuropsychiatric disorders, understanding the role of the PSD proteins in group I mGluR trafficking may provide opportunities for the development of novel therapeutics in multiple neuropsychiatric disorders.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"257-268"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}