Journal of Membrane Biology最新文献_第2页

Design of a Multi-Epitope Vaccine using β-barrel Outer Membrane Proteins Identified in Chlamydia trachomatis. 利用沙眼衣原体β-桶状外膜蛋白设计多表位疫苗。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-09-04 DOI: 10.1007/s00232-025-00360-5

Amisha Panda, Jahnvi Kapoor, B Hareramadas, Ilmas Naqvi, Satish Ganta, Ravindresh Chhabra, Sanjiv Kumar, Anannya Bandyopadhyay

{"title":"Design of a Multi-Epitope Vaccine using β-barrel Outer Membrane Proteins Identified in Chlamydia trachomatis.","authors":"Amisha Panda, Jahnvi Kapoor, B Hareramadas, Ilmas Naqvi, Satish Ganta, Ravindresh Chhabra, Sanjiv Kumar, Anannya Bandyopadhyay","doi":"10.1007/s00232-025-00360-5","DOIUrl":"https://doi.org/10.1007/s00232-025-00360-5","url":null,"abstract":"Chlamydia trachomatis is an obligate intracellular Gram-negative pathogen that causes sexually transmitted infections (STIs) and trachoma. Current interventions are limited due to the widespread nature of asymptomatic infections, and the absence of a licensed vaccine exacerbates the challenge. In this study, we predicted outer membrane β-barrel (OMBB) proteins and designed a multi-epitope vaccine (MEV) construct using identified proteins. We employed a consensus-based computational framework on the C. trachomatis D/UW-3/CX proteome and identified 17 OMBB proteins, including well-known Pmp family members and MOMP. Eight OMBB proteins were computationally characterized, showing significant structural homology with known outer membrane proteins from other bacteria. Sequence-based annotation tools were used to determine their putative functions. B-cell and T-cell epitopes were predicted from the selected proteins. The MEV construct was designed using four cytotoxic T-lymphocyte (CTL) epitopes and 29 helper T-lymphocyte (HTL) epitopes from six OMBB proteins, which were conserved across 106 C. trachomatis serovars. To enhance its immunogenicity, the vaccine was supplemented with the Cholera toxin B subunit and PADRE sequence at the N-terminus. The MEV construct, of length 780 amino acids, was predicted to be antigenic, non-allergenic, non-toxic, and soluble. Secondary structure analysis revealed 95% random coils. A three-dimensional structural model of the MEV was generated and subsequently validated. Molecular docking between MEV and toll-like receptor 4 (TLR4) revealed strong and stable binding interactions. The MEV-TLR4 complex was found to be structurally compact and stable using molecular dynamics simulation. Immune simulation of the MEV construct elicited a strong immune response. This study highlights OMBB proteins as promising immunogenic targets and presents a computationally designed MEV candidate for C. trachomatis infection.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994128","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}

引用次数: 0

Hypoxia Modulates Membrane Mechanics in Pancreatic Cancer. 缺氧调节胰腺癌的膜力学。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-18 DOI: 10.1007/s00232-025-00358-z

Prema Kumari Agarwala, Shobhna Kapoor

{"title":"Hypoxia Modulates Membrane Mechanics in Pancreatic Cancer.","authors":"Prema Kumari Agarwala, Shobhna Kapoor","doi":"10.1007/s00232-025-00358-z","DOIUrl":"https://doi.org/10.1007/s00232-025-00358-z","url":null,"abstract":"Aggressive cancer cells such as pancreatic cells exhibit an enhanced metastatic phenotype that involves cell migration and invasion. Cellular membrane deformation is a key process implicit in cell movement. This implicates a link between altered lipid metabolism during cancer progression and modulated membrane properties and hence associated functions. One of the key factors underlying the aggressiveness of pancreatic cancer is the presence of the highest percentage of hypoxia, which further adds to the lipid metabolic reprogramming. The subsequent effect of hypoxia-induced lipidome changes on membrane properties governing cell movement was investigated in this work using a combination of cell biology, microscopy, and spectroscopy. Our findings revealed that hypoxia induces distinct lipidome signatures in a cell-line-dependent fashion, which in turn differentially modulates the cell membrane stiffness. The correlation of cell stiffness with other membrane properties and the actin cytoskeleton shows a random correlation indicating that hypoxic stress distinctly regulates specific membrane attributes governing cellular functioning and should be consulted for the development of effective treatments for pancreatic cancer.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876537","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}

引用次数: 0

Pore Formation by Pore Forming Proteins in Lipid Membranes: Structural Insights Through Cryo-EM. 脂质膜中孔隙形成蛋白的孔隙形成：通过低温电子显微镜观察结构。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 Epub Date: 2025-03-28 DOI: 10.1007/s00232-025-00344-5

Arnab Chatterjee, Prasenjit Naskar, Suman Mishra, Somnath Dutta

{"title":"Pore Formation by Pore Forming Proteins in Lipid Membranes: Structural Insights Through Cryo-EM.","authors":"Arnab Chatterjee, Prasenjit Naskar, Suman Mishra, Somnath Dutta","doi":"10.1007/s00232-025-00344-5","DOIUrl":"10.1007/s00232-025-00344-5","url":null,"abstract":"Many pathogenic bacteria utilize their complicated appalling arsenal, bacterial virulence factors, to attack host cells by damaging the host cell membrane and neutralizing host defense mechanisms. Bacterial pore-forming proteins (PFPs) are one of them, they include a distinct class of secreted soluble toxin monomers, which binds to the specific cell surface receptors and /or lipids, oligomerizes as an amphipathic transmembrane pore complex on host cell membranes, and deforms the integrity of the plasma membrane. Researchers have focused on characterizing the structure and function of different Pore Forming Toxins (PFTs) from various organisms, where most of the structural studies employed X-ray crystallography, single-particle cryo-EM, and cryo-electron tomography. However, historically, most of these previous studies focused on using detergent to solubilize and oligomerize the PFTs. Additionally, previous studies have also shown that lipid membranes and lipid components, including cell surface receptors, play a critical role in pore formation and oligomerization. However, there are limited studies available that aim to resolve the structure and function of PFTs in liposomes. In this review article, we majorly focused on structural and functional studies of pore-forming toxins in the presence of detergents, lipid nanodiscs, and liposomes. We will also discuss the challenges and benefits of using liposomes to study pore-forming proteins in more biologically relevant membrane environments.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"305-322"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744156","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}

引用次数: 0

Action of the Terminal Complement Pathway on Cell Membranes. 终末补体途径对细胞膜的作用。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 Epub Date: 2025-03-23 DOI: 10.1007/s00232-025-00343-6

Bill H T Ho, Bradley A Spicer, Michelle A Dunstone

{"title":"Action of the Terminal Complement Pathway on Cell Membranes.","authors":"Bill H T Ho, Bradley A Spicer, Michelle A Dunstone","doi":"10.1007/s00232-025-00343-6","DOIUrl":"10.1007/s00232-025-00343-6","url":null,"abstract":"The complement pathway is one of the most ancient elements of the host's innate response and includes a set of protein effectors that rapidly react against pathogens. The late stages of the complement reaction are broadly categorised into two major outcomes. Firstly, C5a receptors, expressed on membranes of host cells, are activated by C5a to generate pro-inflammatory responses. Secondly, target cells are lysed by a hetero-oligomeric pore known as the membrane attack complex (MAC) that punctures the cellular membrane, causing ion and osmotic flux. Generally, several membrane-bound and soluble inhibitors protect the host membrane from complement damage. This includes inhibitors against the MAC, such as clusterin and CD59. This review addresses the most recent molecular and structural insights behind the activation and modulation of the integral membrane proteins, the C5a receptors (C5aR1 and C5aR2), as well as the regulation of MAC assembly. The second aspect of the review focuses on the molecular basis behind inflammatory diseases that are reflective of failure to regulate the terminal complement effectors. Although each arm is unique in its function, both pathways may share similar outcomes in these diseases. As such, the review outlines potential synergy and crosstalk between C5a receptor activation and MAC-mediated cellular responses.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"269-304"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Introduction to Special Issue on Role of Membranes in the Pore-Formation Mechanism of Pore-Forming Proteins and Toxins. 《膜在成孔蛋白和毒素的成孔机制中的作用》特刊导论。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 DOI: 10.1007/s00232-025-00353-4

Kausik Chattopadhyay

引用次数: 0

Oxysterols Outcompete Cholesterol Binding to the Membrane-Inserted Cytolysin A Pore Complex. 氧甾醇与胆固醇在膜插入细胞溶解素A孔复合物上的结合。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1007/s00232-025-00349-0

Samlesh Choudhury, Bharath Desikan, K Ganapathy Ayappa

{"title":"Oxysterols Outcompete Cholesterol Binding to the Membrane-Inserted Cytolysin A Pore Complex.","authors":"Samlesh Choudhury, Bharath Desikan, K Ganapathy Ayappa","doi":"10.1007/s00232-025-00349-0","DOIUrl":"10.1007/s00232-025-00349-0","url":null,"abstract":"Pore-forming toxins (PFTs) belong to a class of proteins expressed by bacteria to initiate infections by unregulated pore formation on the plasma membrane of host cells. Although cholesterol is a key sterol motif that promotes toxin activity, the influence of oxysterols, upregulated in senescent cells or in other inflammatory disorders, on lytic activity has not received much attention. Using all-atom molecular dynamics simulations, we study the changes to the sterol binding landscape of membrane-inserted cytolysin A (ClyA), an <math><mi>α</mi></math> -PFT expressed by E. coli, in the presence of tail-oxidized 25-hydroxycholesterol (25-HC) in a palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:25-HC (70:20:10) membrane. 25-HC was found to entirely replace previously identified cholesterol binding hotspots [PNAS,115 7323-7330] between the membrane-inserted <math><mi>β</mi></math> -tongue motifs with binding lifetimes on the order of microseconds. Although the overall sterol occupancy is lower for the N-terminal helix motif that forms the lining of the water channel, 25-HC binding is less when compared with cholesterol. The presence of the additional OH group on the 25th carbon enhances interactions with polar residues of the <math><mi>β</mi></math> -tongue, increasing 25-HC binding times by several fold when compared with cholesterol. We discuss the implications of this enhanced oxysterol interaction on pore formation of the <math><mi>α</mi></math> family of toxins such as ClyA, in contrast with the cholesterol-dependent cytolysins, where oxysterols have been shown to be detrimental to pore formation.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"341-352"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250608","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}

引用次数: 0

Correction to: Introduction to Special Issue on Role of Membranes in the Pore-Formation Mechanism of Pore-Forming Proteins and Toxins. 更正：《膜在成孔蛋白和毒素的成孔机制中的作用》特刊导言。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 DOI: 10.1007/s00232-025-00356-1

Kausik Chattopadhyay

引用次数: 0

Hetero-Oligomeric Protein Pores for Single-Molecule Sensing. 用于单分子传感的异聚寡聚蛋白孔。

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 Epub Date: 2024-12-19 DOI: 10.1007/s00232-024-00331-2

Remya Satheesan, Asuma Janeena, Kozhinjampara R Mahendran

{"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":"10.1007/s00232-024-00331-2","url":null,"abstract":"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.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"257-267"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","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}

引用次数: 0

Interaction of an Oomycete Nep1-like Cytolysin with Natural and Plant Cell-Mimicking Membranes. 一种类似于卵菌 Nep1 的细胞溶解素与天然膜和植物细胞模拟膜的相互作用

IF 2.9 4区生物学

Journal of Membrane Biology Pub Date : 2025-08-01 Epub Date: 2024-12-18 DOI: 10.1007/s00232-024-00330-3

Tina Snoj, Tjaša Lukan, Kristina Gruden, Gregor Anderluh

{"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":"10.1007/s00232-024-00330-3","url":null,"abstract":"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, NLPPya, 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 NLPPya is concentration- and time-dependent, confirm the small size of the pores by observing the inability of NLPPya monomers to pass through them, image the morphological changes of GUVs at higher concentrations of NLPPya and confirm its oligomerization on the membrane of GUVs. In addition, NLPPya bound to plasma membranes of protoplasts, which showed varying responses. Our results provide new insights into the interaction of NLPPya with model lipid membranes containing plant-derived sphingolipids.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"323-339"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313774/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Insights into Interactions between Ofloxacin and Ionic Micelles. 氧氟沙星与离子胶束相互作用的分子研究。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2025-07-22 DOI: 10.1007/s00232-025-00357-0

Saqib Rabbani, Areesha Maryam, Muhammad Sohail, Athar Yaseen Khan

{"title":"Molecular Insights into Interactions between Ofloxacin and Ionic Micelles.","authors":"Saqib Rabbani, Areesha Maryam, Muhammad Sohail, Athar Yaseen Khan","doi":"10.1007/s00232-025-00357-0","DOIUrl":"https://doi.org/10.1007/s00232-025-00357-0","url":null,"abstract":"The growing antimicrobial resistance presents a challenge in developing new potent drugs, but this effort is hindered by a lack of information regarding how these new drugs would behave in biomembranes. Surfactants are considered mimetic models for biomembranes and can be used to study drug-membrane interactions. In this study, we used two well-known surfactants-cationic cetyltrimethylammonium bromide and anionic sodium dodecyl sulfate-as model membranes to investigate their interaction with the antimicrobial drug ofloxacin (OFL). These interactions were studied using volumetric and acoustic methods over the temperature range of 293.15-323.15 K to determine the apparent molar volume, isentropic compressibility, apparent molar compressibility, acoustic impedance, relative association, and intermolecular free length. Furthermore, UV-Vis spectroscopy and cyclic voltammetry were employed to evaluate the binding constants and free energies of the drug-surfactant systems. These results provide key molecular insights into the thermodynamics of OFL partitioning and its binding mechanisms with amphiphilic assemblies. Such mechanistic understanding is crucial for the rational design of antibiotic delivery systems, facilitating precise control over drug loading and release dynamics in surfactant-based formulations.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692248","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}

引用次数: 0