Biochimica et biophysica acta. Biomembranes最新文献

{"title":"Examining the thermotropic properties of large circularized nanodiscs","authors":"Mark J. Arcario ,&nbsp;Vikram Dalal ,&nbsp;David Fan ,&nbsp;Fong-Fu Hsu ,&nbsp;Wayland W.L. Cheng","doi":"10.1016/j.bbamem.2025.184451","DOIUrl":"10.1016/j.bbamem.2025.184451","url":null,"abstract":"<div><div>Nanodiscs, soluble membrane mimetics composed of an amphipathic membrane scaffold protein encircling a lipid bilayer, are widely used in biophysical and structural studies of membrane proteins. Because many membrane proteins are responsive to their membrane environment, through specific protein–lipid interactions and bulk membrane shape and structure, it is important to understand the properties of lipid bilayers contained within nanodiscs in order to interpret studies using this technology. Nanodiscs are known to alter lipid properties, such as membrane thickness and melting temperature, and interactions with the nanodisc rim have been hypothesized to produce local perturbations in lipid structure and dynamics. Larger nanodiscs should compensate for this effect with a larger unperturbed area. To test this hypothesis, we examined the lipid bilayer properties of several lipids (DMPC, DPPC, POPC, DSPC) and soy polar lipid in circularized nanodiscs of 11 nm to 50 nm diameter using the environmentally-sensitive fluorophore, Laurdan. In nanodiscs containing a single lipid type, as nanodisc size increased, lipid packing, melting temperature, and cooperativity better approximated the properties of that lipid in large unilamellar vesicles (LUVs). In spNW50 (50 nm nanodisc), the lipid packing and melting temperature were indistinguishable from LUVs. However, nanodiscs containing soy polar lipids did not follow this trend suggesting that complex lipid mixtures may produce preferential incorporation of lipids into the nanodisc or nonhomogeneous distribution of lipids within the nanodisc.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184451"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046028","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 coronavirus spike HR2 domain: An obscure player entering the limelight during membrane fusion?","authors":"Elena T. Aliper ,&nbsp;Roman G. Efremov","doi":"10.1016/j.bbamem.2025.184445","DOIUrl":"10.1016/j.bbamem.2025.184445","url":null,"abstract":"<div><div>The coronavirus spike protein, the key entity effectuating membrane fusion, cannot exist without membrane-active fragments. In addition to fusion peptides, among such domains are HR1 and HR2. Crucial to the spike's refolding and membrane fusion, they are believed to both interact with each other and bind to the membranes that are merged. To elucidate HR2's precise role in this process, an understanding of its structure and behaviour is required. Here, we used various computational approaches to study SARS-CoV-2 spike HR2's (1163-1211) interaction with membranes in the context within which it operates in live spike. During simulations with model bilayers, HR2 remained hugely unresponsive to the presence of a membrane, however, when extended to include the transmembrane domain (TMD) (1212-1234) and/or membrane-active preHR2 fragment (1147-1161), HR2’s binding to model bilayers was markedly enhanced. The trimeric coiled-coil of HR2 does not dissociate either on its own or with added TMD and/or preHR2. Molecular hydrophobicity potential (MHP) mapping showed that HR2's central part possesses a tilted oblique-oriented motif characteristic of “textbook” membrane-active peptides, albeit flanked by highly hydrophilic fragments. A truncated HR2 only encompassing this motif had a greater affinity for membranes, suggesting HR2 has a modular structure with a membrane-active segment masked by flanking regions and might be potentiated by HR2-adjacent domains and other factors coming into play after the spike gets enzymatically cleaved. Such a modular structure may have evolved for HR2's membrane activity to be regulated very subtly and “switched on” at precisely the right moment during viral fusion.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184445"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933285","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":"Antileishmanial, cytotoxic activities, and membrane rigidity effects of three synthetic compounds","authors":"Éder Jéferson Souza Cardoso ,&nbsp;Ellyêssa Nascimento Borges ,&nbsp;Kleber Santiago Freitas e Silva ,&nbsp;Rodrigo Saar Gomes ,&nbsp;Fabiana Taniguchi Boni ,&nbsp;Jhon Kennedy Alves Pereira ,&nbsp;Paula Maria Alexandre Mangoba ,&nbsp;Luciano Morais Lião ,&nbsp;Ricardo Menegatti ,&nbsp;Antonio Alonso","doi":"10.1016/j.bbamem.2025.184450","DOIUrl":"10.1016/j.bbamem.2025.184450","url":null,"abstract":"<div><div>Three antileishmanial compounds incorporating a butylated hydroxytoluene (BHT) moiety and an acrylate-based Michael acceptor scaffold were rationally designed from the lead structures LQFM064 and LQFM332, which feature a chalcone-derived core. Their activities against <em>Leishmania</em> (<em>L</em>.) <em>amazonensis</em> were evaluated. Acrylate derivatives (<strong>5</strong>), (<strong>6</strong>), and (<strong>7</strong>) displayed IC₅₀ values comparable to miltefosine, while showing markedly lower cytotoxicity toward J774.A1 and differentiated THP-1 macrophages, along with reduced hemolytic potential. Spin-label electron paramagnetic resonance (EPR) spectroscopy revealed that treatment with these compounds induces membrane rigidity after 24 h in a concentration-dependent manner. This effect is unlikely due to direct membrane interaction, as it does not occur after short incubations or at low concentrations, suggesting a correlation with oxidative stress, such as lipid peroxidation and/or protein oxidation, likely triggered by elevated reactive oxygen species (ROS) production. In contrast, no oxidative stress-induced membrane rigidity was detected in uninfected macrophages, suggesting that nitric oxide production may mitigate oxidative damage in these cells. However, significant membrane rigidity was observed in <em>Leishmania</em>-infected macrophages at concentrations slightly above the IC₅₀ for amastigotes, indicating that the compounds may selectively target infected macrophages. Additionally, compound (<strong>5</strong>) exhibited moderate cytotoxicity in the rapidly proliferating J774.A1 macrophage line but displayed very low cytotoxicity in differentiated, non-proliferative THP-1 macrophages. Overall, this study suggests that the primary mechanisms underlying the antileishmanial activity of these compounds are associated with their effects on the parasite plasma membrane, potentially leading to ionic leakage, subsequent disruption of mitochondrial membrane potential, and enhanced ROS generation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184450"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010033","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":"Evaluation of the effects of bovine lactoferrin on the membrane of human erythrocytes","authors":"Leilismara Sousa Nogueira ,&nbsp;Bárbara Martins Cordeiro ,&nbsp;Gilvânia Aparecida Rabelo Cordeiro ,&nbsp;Ana Carolina Pacheco Ramos ,&nbsp;Douglas Donizetti Raimundo ,&nbsp;Grazielle Aparecida Silva Maia ,&nbsp;Cristiane de Oliveira Renó ,&nbsp;Leonardo Nunes Medeiros ,&nbsp;Luciana Estéfani Drumont Carvalho ,&nbsp;Vanessa Faria Cortes ,&nbsp;Hérica de Lima Santos ,&nbsp;Carlos Frederico Leite Fontes ,&nbsp;Leandro Augusto Barbosa","doi":"10.1016/j.bbamem.2025.184455","DOIUrl":"10.1016/j.bbamem.2025.184455","url":null,"abstract":"<div><div>Lactoferrin (Lf) is an iron-binding glycoprotein involved in various biological functions, including iron metabolism and immune response. Bovine lactoferrin (bLf) has gained attention due to its potential therapeutic applications. This study investigates the effects of bLf on human erythrocyte membranes, focusing on Na,K-ATPase (NKA) modulation. Whole blood and erythrocyte ghost membranes were treated with different concentrations of bLf, and multiple assays were performed to assess enzyme activity, lipid peroxidation, and lipid membrane composition. First, we demonstrate that Fe⁺² is not able to increase the activity of the NKA. Bovine lactoferrin, on the other hand, significantly increases NKA activity, particularly affecting the α3 isoform. Additionally, bLf treatment led to an increase in total phospholipids and cholesterol content, suggesting modifications in the erythrocyte membrane. Molecular docking analysis revealed a strong interaction between bLf and α3-NKA, but not α1 isoform, supporting a potential regulatory role. Furthermore, bLf reduced Fe³⁺ and Thiobarbituric Acid Reactive Substances (TBARS) levels, indicating a protective effect against oxidative stress. These findings suggest that bLf modulates erythrocyte membrane properties, and could be specific to α3-NKA activation, reinforcing the role of Fe⁺³ in modulating the NKA activity.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184455"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032579","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":"Daptomycin membrane activity is modulated by the localized interplay between calcium ions and phospholipids in monolayers and bilayers containing a lysyl-phosphatidylglycerol analogue","authors":"Maria Hoernke ,&nbsp;Shuai Shi ,&nbsp;Alasdair T.M. Hubbard ,&nbsp;Nina Geringer ,&nbsp;Fabio Strati ,&nbsp;Chen Shen ,&nbsp;Christian Wölk ,&nbsp;Richard D. Harvey","doi":"10.1016/j.bbamem.2025.184452","DOIUrl":"10.1016/j.bbamem.2025.184452","url":null,"abstract":"<div><div>Using the stable synthetic analogue 3-aza-dehydroxylysyl-phosphatidylglycerol (3adLPG), the putative role of native staphylococcal LPG in inhibiting the antibiotic daptomycin from binding to its target phosphatidylglycerol (PG), was investigated with respect to interfacial interactions between these lipids, daptomycin, and calcium ions. The influence of lipid monolayer/bilayer composition and interfacial ion concentrations upon the structure and integrity of model membranes were probed after daptomycin challenge using a combination of surface x-ray scattering techniques and fluorescence assays. In models representing the membrane composition of the daptomycin susceptible phenotype consisting of PG/3adLPG in a 7:3 M ratio, calcium ions drive the formation of two separate phases; Ca²⁺ cross-linked PG/PG pairs and PG/3adLPG ion pairs. Daptomycin is able to bind directly to the lipids in the PG/PG phase and increases the amount of interfacial Ca²⁺ ions to a level sufficient to displace 3adLPG from ion pairs with PG, and thus binds to its target PG. In bilayers with mixed chain lipids, daptomycin leads to pronounced membrane perturbations and enhanced permeability. Sequestering all of the available PG into PG/3adLPG ion pairs, therefore, would represent a putative daptomycin non-susceptible membrane. Daptomycin binding and the extent of subsequent lipid structural changes are reduced in these membranes. This implies that in bacteria, native LPG biosynthesis would need to ensure either an equivalence or an excess in relation to membrane PG content, in order for this mechanism alone to significantly contribute to daptomycin resistance.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184452"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032551","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":"Biophysical investigations of the membrane interactions of collagen VI-derived host defense peptides","authors":"Kathakali De ,&nbsp;Karin Bryder ,&nbsp;Christopher Aisenbrey ,&nbsp;Matthias Mörgelin ,&nbsp;Burkhard Bechinger","doi":"10.1016/j.bbamem.2025.184448","DOIUrl":"10.1016/j.bbamem.2025.184448","url":null,"abstract":"<div><div>Collagen VI is an extracellular matrix protein forming complex microfibrillar networks in connective tissues. Specifically, we focused on its role in innate immunity, in particular on cationic sequence motifs from the α3(VI)-chain, which exhibit strong antibacterial properties against both Gram-positive and Gram-negative bacteria <em>in vitro</em> and <em>in vivo</em>. Cytotoxicity assays revealed minimal to no adverse effects, even at concentrations effective against bacterial pathogens. This favorable safety profile suggests that these antimicrobial peptides selectively target bacterial membranes while sparing host cells, making them promising candidates for therapeutic development.</div><div>The membrane structure and interactions of two antimicrobial peptides were investigated in quantitative detail using solid-state NMR, CD and fluorescence spectroscopies. Whereas calcein release was somewhat more pronounced from POPE/POPG 3/1 vesicles when compared to POPC/30 % cholesterol, this activity is about two orders of magnitude increased when POPC/POPG 3/1 liposomes are investigated. This pronounced lipid dependence was reproduced with magainin 2, a well-known linear cationic AMP. In lipid titration experiments both collagen-derived peptides showed a transition from predominantly random coil to helical conformations. Quantitative evaluation of membrane association required the presence of PEG-lipids which are known to prevent the agglutination of POPE/POPG 3/1 liposomes. A dissociation constant in the 260 μM range was observed for GVR28 while the binding isotherms reveal an intermediate state when SFV33 associates with bacterial membranes. ²H solid-state NMR reveals considerable membrane disorder of the deuterated PG palmitoyl chain in POPE/POPG membranes. The ensemble of biophysical data suggests two distinct modes of action for the collagen derived peptides.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184448"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940697","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":"Order parameters in membranes: Following Joachim Seelig's path","authors":"Estelle Morvan ,&nbsp;Axelle Grélard ,&nbsp;Erick J. Dufourc","doi":"10.1016/j.bbamem.2025.184449","DOIUrl":"10.1016/j.bbamem.2025.184449","url":null,"abstract":"<div><div>Following the publication of biological membrane models in the 1970s, Joachim Seelig was the first to experimentally demonstrate the dynamic nature of these membranes. He conducted the first ssNMR experiments to measure the order parameters of the C<img>D (²H) bond of lipids deuterium-labelled, showing a fairly fluid membrane interior. Since then, the order parameters of the C<img>D, C<img>H and C<img>C bonds have been measured. They can be used to describe the dynamics of membranes on several space and time scales: intramolecular (<em>Å</em>/<em>ns-ps</em>), molecular (<em>nm/</em><em>ns</em><em>–100 ns</em>) and collective (membrane deformations, μm<em>/</em>μs). The profile of C<img>D, C<img>H, C<img>C order parameters across the membrane bilayer allows us to describe the lipid membrane as being very rigid at the glycerol and chain levels and very fluid at its center and surface. This is true for lipid chains carrying double bonds, rings or branched methyl groups. Bipolar lipids that span the entire membrane do not have a very fluid membrane interior. Sterols modulate membrane dynamics, increasing order parameters in the fluid phase and decreasing them in the gel phases. They can be described as regulators of membrane dynamics, as they maintain the membrane in a dynamic state that varies very little when environmental factors change (temperature, pH, etc.). The description of order parameters by statistical mechanics allows the length of the chains, the thickness of the bilayer and the membrane elastic constants to be calculated accurately. The surface area of each lipid in the membrane can also be calculated from the <em>plateau</em> of order parameters (positions C3-C10): <span><math><mfenced><msub><mi>A</mi><mi>L</mi></msub></mfenced><mo>=</mo><mn>83</mn><mfenced><mrow><mn>1</mn><mo>−</mo><mfenced><msubsup><mi>S</mi><mi>CD</mi><mi>plat</mi></msubsup></mfenced></mrow></mfenced></math></span>.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184449"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940705","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":"Steady dimer formation by the S31N mutant of influenza A virus M2 protein in living cell membranes","authors":"Kenichi Kawano ,&nbsp;Tyuji Hoshino ,&nbsp;Yoshiaki Yano ,&nbsp;Katsumi Matsuzaki","doi":"10.1016/j.bbamem.2025.184456","DOIUrl":"10.1016/j.bbamem.2025.184456","url":null,"abstract":"<div><div>The integral matrix protein M2 of the influenza A virus (H3N2) has been proposed to form a proton-selective channel, and is a target of the antiviral drug amantadine hydrochloride (Am). A significant increase in the number of drug-resistant strains containing the predominant M2-S31N mutant have emerged. We have previously developed a stoichiometric analysis of oligomeric states of membrane proteins by utilizing a coiled-coil method and fluorescence resonance energy transfer phenomenon and demonstrated that full-length M2-WT proteins in living cells formed a dimer at neutral pH, which was converted to a tetramer at acidic pH. In the present study, we revealed that the M2-S31N mutant stably formed dimers independent of pH, which was stabilized by multiple interactions between the protomers. We also found that neither the channel activity nor the oligomeric state of S31N were affected by Am. Molecular dynamics (MD) simulations revealed that Asn31 and Ile35 are involved in proton conduction <em>via</em> steady interactions with cholesterol. These results indicate that Am resistance could be attributed to a change in the arrangement of helices interfering with drug binding.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184456"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038976","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":"Complexes of star-shaped block copolymers of poly(2-alkyl-2-oxazine)s and curcumin can affect lipid bilayers mimicking biomembranes","authors":"Svetlana S. Efimova ,&nbsp;Vera A. Martynyuk ,&nbsp;Nina D. Kozina ,&nbsp;Tatyana Y. Kirila ,&nbsp;Alexander P. Filippov ,&nbsp;Olga S. Ostroumova","doi":"10.1016/j.bbamem.2025.184443","DOIUrl":"10.1016/j.bbamem.2025.184443","url":null,"abstract":"<div><div>Poly(2-alkyl-2-oxazine)s (PAlOz) are promising tools for developing delivery systems due to their high biocompatibility, resistance to enzyme hydrolysis, and ability to degrade in biological environments. Here, we investigated the effects of hexaaza[2₆]cyclophane (CPh6), poly(2-methyl-2-oxazine) (PMedOz), a block copolymer of poly(2-ethyl-2-oxazine) (PEtOz) and poly(2-isopropyl-2-oxazine) (PiPrOz), star-shaped block copolymers with six PAlOz arms and a CPh6 branching center (CPh6-PAlOz), and the complexes of all these macromolecules with curcumin on lipid bilayers mimicking the membranes of normal and cancer cells. Curcumin alone demonstrated a pronounced ability to reduce the boundary potential of lipid bilayers composed of phosphatidylcholine or phosphatidylserine, while PMedOz and PEtOz-b-PiPrOz copolymers exhibited either no or weak effects on the electrical properties of biomimetic model membranes. CPh6-PAlOz star-shaped block copolymers were able to interact with K⁺-nonactin. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane lipids indicated that curcumin and all tested macromolecules had more pronounced effects on phosphatidylserine melting than on the phase behavior of phosphatidylcholine. A star-shaped block copolymer with a [PEtOz]/[PiPrOz] ration of 0.8 significantly decreased the melting point of phosphatidylserine. The disordering effects of complexes of curcumin with CPh6, PEtOz-b-PiPrOz copolymers, or the CPh6-PAlOz star-shaped block copolymer with a [PEtOz]/[PiPrOz] ratio of 5 on phosphatidylserine bilayers were less than the algebraic sum of the effects of the polymers and curcumin separately. These data indicate that the carrier cannot be considered an inert matrix that does not affect the biological activity of the transferred active compound, and this should be taken into account when assessing the biological consequences.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184443"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895469","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":"SARS-CoV E protein couples asymmetric leaflet thickness and curvature deformations","authors":"Jesse W. Sandberg ,&nbsp;Grace Brannigan","doi":"10.1016/j.bbamem.2025.184447","DOIUrl":"10.1016/j.bbamem.2025.184447","url":null,"abstract":"<div><div>The Envelope protein (E protein) of SARS-CoVs 1 and 2 has been implicated in the viral budding process and maintaining the spherical shape of the virus, but direct evidence linking the protein to long-range membrane deformation is still lacking. Computational predictions from molecular simulation have offered conflicting results, some showing long-range E-induced membrane curvature and others showing only local deformations. In the present study, we determine the mechanism driving these deformations by modulating the degree of hydrophobic mismatch between protein and membrane. We observe that certain barostat and restraint settings, common in coarse-grained MD simulations, can prevent equilibration of the membrane area. Our results indicate that the E protein does not induce long-range curvature, but does exhibit severe local deformations that are exacerbated by hydrophobic mismatch. These deformations occur in conjunction with local leaflet thickness asymmetry, suggesting asymmetry and curvature couple to reduce the free energy cost of a deformed membrane.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 8","pages":"Article 184447"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026664","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}