Journal of Membrane Biology最新文献

{"title":"Effects of Chemical Fixatives on Kinetic Measurements of Biomolecular Interaction on Cell Membrane.","authors":"Tianbao Dong, Shengyang Wan, Yanhui Wang, Yaru Fu, Pengcheng Wang","doi":"10.1007/s00232-024-00305-4","DOIUrl":"10.1007/s00232-024-00305-4","url":null,"abstract":"<p><p>Understanding the interaction between ligands and membrane proteins is important for drug design and optimization. Although investigation using live cells is desirable, it is not feasible in some circumstances and cell fixation is performed to reduce cell motion and degradation. This study compared the effects of five fixatives, i.e., formaldehyde vapor (FV), paraformaldehyde (PFA), acetone, methanol, and ethanol, on kinetic measurements via the LigandTracer method. We found that all five fixatives exerted insignificant effects on lectin-glycan interaction. However, antibody-receptor interaction is markedly perturbed by coagulant fixatives. The acetone fixation changed the binding of the anti-human epidermal growth factor receptor 2 (HER2) antibody to HER2 on the cell membrane from a 1:2 to a 1:1 binding model, while methanol and ethanol abolished the antibody binding possibly by removal of the HER2 receptors on the cell membrane. The capability of binding was retained when methanol fixation was performed at lower temperatures, albeit with a binding model of 1:1 instead. Moreover, whereas cell morphology does not exert a substantial impact on lectin-glycan interaction, it can indeed modify the binding model of antibody-receptor interaction. Our results provided insights into the selection of fixatives for cell-based kinetic studies.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418385","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":"Identification of Prognostic and Immune Characteristics of Two Lung Adenocarcinoma Subtypes Based on TRPV Channel Family Genes.","authors":"Jianhua Jiang, Pengchao Zheng, Lei Li","doi":"10.1007/s00232-023-00300-1","DOIUrl":"10.1007/s00232-023-00300-1","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is one of the deadliest malignant tumors worldwide. Transient receptor potential vanilloid (TRPV) channels take pivotal parts in many cancers, but their impact on LUAD remains unexplored. In this study, LUAD samples were classified into two subtypes according to the expression characteristics of TRPV1-6 genes, with LUAD subtype cluster2 exhibiting significantly higher survival rates than cluster1. Subsequently, analysis of differentially expressed genes (DEGs) was performed between cluster1 and cluster2, revealing enrichment of DEGs in channel activity and Ca²⁺ signaling pathways. We established a protein-protein interaction network based on DEGs and constructed a LUAD prognostic model by using Cox regression analysis based on genes corresponding to 170 protein nodes. The prognostic model demonstrated good predictive ability for patient prognosis, with higher survival rates observed in the low-risk (LR) group. The risk score was validated as an independent prognostic indicator, according to Cox regression analysis. A clinically applicable nomogram was plotted. Immunological analysis indicated that the LR and high-risk (HR) groups had varied proportions of immune cell infiltration. The immunotherapy prediction indicated that LUAD patients in LR group had a greater likelihood to benefit from immune checkpoint blockade therapy. Furthermore, we hypothesized that the expression patterns of feature genes in the LUAD model were related to the sensitivity to lung cancer therapeutic drugs TAS-6417 and Erlotinib. To sum up, our LUAD prognostic model possessed clinical applicability for prognosis and immunotherapy response prediction.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040829","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":"Correction: Role of Hydrophobic Amino-Acid Side-Chains in the Narrow Selectivity Filter of the CFTR Chloride Channel Pore in Conductance and Selectivity.","authors":"Paul Linsdell","doi":"10.1007/s00232-023-00304-x","DOIUrl":"10.1007/s00232-023-00304-x","url":null,"abstract":"","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513496","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 γ-Oryzanol on the LE-LC Phase Coexistence Region of DPPC Langmuir Monolayer.","authors":"Raghavendra, Bharat Kumar, Siva N Chari","doi":"10.1007/s00232-023-00288-8","DOIUrl":"10.1007/s00232-023-00288-8","url":null,"abstract":"<p><p>We have studied the effect of relative composition of γ-Oryzanol (γ-Or) on the liquid expanded-liquid condensed phase coexistence region in the mixed Langmuir monolayer of γ-Or and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules at air-water interface. The surface manometry studies at a fixed temperature show that the mixture of γ-Or and DPPC forms a stable monolayer at air-water interface. As the relative composition of γ-Or increases the range of area per molecule over which the coexistence of liquid expanded (LE)-liquid condensed (LC) phases exists reduces. Although the LE-LC phase coexistence corresponds to the first-order phase transition, the slope of the surface pressure-area per molecule isotherm is non-zero. Earlier studies have attributed the non-zero slope in LE-LC phase coexistence region to the influence of the strain between the ordered LC phase and disordered LE phase. The effect of strain on the coexistence of LE-LC phases can be studied in terms of molecular density-strain coupling. Our analysis of the liquid condensed-liquid expanded coexistence region in the isotherms of mixed monolayers of DPPC and γ-Or shows that with the increase in the mole fraction of sterol in the mixed monolayer the molecular lateral density-strain coupling increases. However, at 0.6 mole fraction of γ-Or in the mixed monolayer the coupling decreases. This is corroborated by the observation of minimum Gibb's free energy of the mixed monolayer at this relative composition of γ-Or indicating better packing of molecules.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572432","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 Functionality of Membrane-Inserting Proteins and Peptides: Curvature Sensing, Generation, and Pore Formation.","authors":"Chandra Has, Sovan Lal Das","doi":"10.1007/s00232-023-00289-7","DOIUrl":"10.1007/s00232-023-00289-7","url":null,"abstract":"<p><p>Proteins and peptides with hydrophobic and amphiphilic segments are responsible for many biological functions. The sensing and generation of membrane curvature are the functions of several protein domains or motifs. While some specific membrane proteins play an essential role in controlling the curvature of distinct intracellular membranes, others participate in various cellular processes such as clathrin-mediated endocytosis, where several proteins sort themselves at the neck of the membrane bud. A few membrane-inserting proteins form nanopores that permeate selective ions and water to cross the membrane. In addition, many natural and synthetic small peptides and protein toxins disrupt the membrane by inducing nonspecific pores in the membrane. The pore formation causes cell death through the uncontrolled exchange between interior and exterior cellular contents. In this article, we discuss the insertion depth and orientation of protein/peptide helices, and their role as a sensor and inducer of membrane curvature as well as a pore former in the membrane. We anticipate that this extensive review will assist biophysicists to gain insight into curvature sensing, generation, and pore formation by membrane insertion.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178027","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":"Cationic Proteins Rich in Lysine Residue Trigger Formation of Non-bilayer Lipid Phases in Model and Biological Membranes: Biophysical Methods of Study.","authors":"Meiyi Li, Edward S Gasanoff","doi":"10.1007/s00232-023-00292-y","DOIUrl":"10.1007/s00232-023-00292-y","url":null,"abstract":"<p><p>Cationic membrane-active toxins are the most abundant group of proteins in the venom of snakes and insects. Cationic proteins such as cobra venom cytotoxin and bee venom melittin are known for their pharmacological reactions including anticancer and antimicrobial effects which arise from the toxin-induced alteration in the dynamics and structure of plasma membranes and membranes of organelles. It has been established that these cationic toxins trigger the formation of non-bilayer lipid phase transitions in artificial and native mitochondrial membranes. Remarkably, the toxin-induced formation of non-bilayer lipid phase increases at certain conditions mitochondrial ATP synthase activity. This observation opens an intriguing avenue for using cationic toxins in the development of novel drugs for the treatment of cellular energy deficiency caused by aging and diseases. This observation also warrants a thorough investigation of the molecular mechanism(s) of lipid phase polymorphisms triggered by cationic proteins. This article presents a review on the application of powerful biophysical methods such as resonance spectroscopy (³¹P-, ¹H-, ²H-nuclear magnetic resonance, and electron paramagnetic resonance), luminescence, and differential scanning microcalorimetry in studies of non-bilayer lipid phase transitions triggered by cationic proteins in artificial and biological membranes. A phenomenon of the triggered by cationic proteins the non-bilayer lipid phase transitions occurring within 10^-2-10^-11 s is discussed in the context of potential pharmacological applications of cationic proteins. Next to the ATP dimer is an inverted micelle made of cardiolipin that serves as a vehicle for the transport of H⁺ ions from the intra-crista space to the matrix. It is proposed that such inverted micelles are triggered by the high density of H⁺ ions and the cationic proteins rich in lysine residue which compete with the conserved lysine residues of the ATP synthase rotor for binding to cardiolipin in the inner mitochondrial membrane and perturb the bilayer lipid packing of cristae. Phospholipids with a blue polar head represent cardiolipin and those with a red polar head represent other phospholipids found in the crista membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172937","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":"Host Lipid Manipulation by Intracellular Bacteria: Moonlighting for Immune Evasion.","authors":"Naveen Challagundla, Deepti Phadnis, Aakriti Gupta, Reena Agrawal-Rajput","doi":"10.1007/s00232-023-00296-8","DOIUrl":"10.1007/s00232-023-00296-8","url":null,"abstract":"<p><p>Lipids are complex organic molecules that fulfill energy demands and sometimes act as signaling molecules. They are mostly found in membranes, thus playing an important role in membrane trafficking and protecting the cell from external dangers. Based on the composition of the lipids, their fluidity and charge, their interaction with embedded proteins vary greatly. Bacteria can hijack host lipids to satisfy their energy needs or to conceal themselves from host cells. Intracellular bacteria continuously exploit host, from their entry into host cells utilizing host lipid machinery to exiting through the cells. This acquisition of lipids from host cells helps in their disguise mechanism. The current review explores various mechanisms employed by the intracellular bacteria to manipulate and acquire host lipids. It discusses their role in manipulating host membranes and the subsequence impact on the host cells. Modulating these lipids in macrophages not only serve the purpose of the pathogen but also modulates the macrophage energy metabolism and functional state. Additionally, we have explored the intricate pathogenic relationship and the potential prospects of using this knowledge in lipid-based therapeutics to disrupt pathogen dominance.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488203","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":"Track and Field of the Journal of Membrane Biology.","authors":"Alexey S Ladokhin","doi":"10.1007/s00232-023-00298-6","DOIUrl":"10.1007/s00232-023-00298-6","url":null,"abstract":"","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720317","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":"Correction: Hans Ussing Memorial Issue: Epithelial Membrane Transport.","authors":"Stanley G Schultz, Alexander Leaf","doi":"10.1007/s00232-023-00290-0","DOIUrl":"10.1007/s00232-023-00290-0","url":null,"abstract":"","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435147","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":"Exploration of the Catalytic Cycle Dynamics of Vigna Radiata H⁺-Translocating Pyrophosphatases Through Hydrogen-Deuterium Exchange Mass Spectrometry.","authors":"Li-Kun Huang, Yi-Cyuan Huang, Pin-Chuan Chen, Ching-Hung Lee, Shih-Ming Lin, Yuan-Hao Howard Hsu, Rong-Long Pan","doi":"10.1007/s00232-023-00295-9","DOIUrl":"10.1007/s00232-023-00295-9","url":null,"abstract":"<p><p>Vigna radiata H⁺-translocating pyrophosphatases (VrH⁺-PPases, EC 3.6.1.1) are present in various endomembranes of plants, bacteria, archaea, and certain protozoa. They transport H⁺ into the lumen by hydrolyzing pyrophosphate, which is a by-product of many essential anabolic reactions. Although the crystal structure of H⁺-PPases has been elucidated, the H⁺ translocation mechanism of H⁺-PPases in the solution state remains unclear. In this study, we used hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (MS) to investigate the dynamics of H⁺-PPases between the previously proposed R state (resting state, Apo form), I state (intermediate state, bound to a substrate analog), and T state (transient state, bound to inorganic phosphate). When hydrogen was replaced by proteins in deuterium oxide solution, the backbone hydrogen atoms, which were exchanged with deuterium, were identified through MS. Accordingly, we used deuterium uptake to examine the structural dynamics and conformational changes of H⁺-PPases in solution. In the highly conserved substrate binding and proton exit regions, HDX-MS revealed the existence of a compact conformation with deuterium exchange when H⁺-PPases were bound with a substrate analog and product. Thus, a novel working model was developed to elucidate the in situ catalytic mechanism of pyrophosphate hydrolysis and proton transport. In this model, a proton is released in the I state, and the TM5 inner wall serves as a proton piston.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720316","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}