Biochimica et biophysica acta. Biomembranes最新文献

{"title":"A molecular mechanism for how pressure induces interdigitation of phospholipid bilayer membranes","authors":"Masaki Goto ,&nbsp;Shuntaro Yoshida ,&nbsp;Shigeyuki Habara ,&nbsp;Agnieszka Wilk-Kohlbrecher ,&nbsp;Joachim Kohlbrecher ,&nbsp;Nobutake Tamai ,&nbsp;Hitoshi Matsuki","doi":"10.1016/j.bbamem.2024.184385","DOIUrl":"10.1016/j.bbamem.2024.184385","url":null,"abstract":"<div><div>The phase transition from the ripple gel phase to the interdigitated gel phase of bilayers of phosphatidylcholines (PCs) with two saturated long-chain fatty acids under high pressure was investigated by pressure-scanning microscopy, fluorometry, and dynamic light scattering (DLS) measurements. Microscopic observation for giant vesicles (GVs) of distearoyl-PC (DSPC) under high pressure showed that spherical GVs transforms significantly into warped and distorted spherical ones instantaneously at the pressure-induced interdigitation. The fluorescence intensities of amphiphilic probe Prodan and hydrophobic probe Laurdan in the dipalmitoyl-PC (DPPC) bilayer steeply decreased and increased, respectively, at the interdigitation, suggesting that the conformational change of the polar head group of DPPC molecule in the bilayer transiently occurred at the interdigitation. Further, it was found from the high-pressure DLS measurements that the size of the vesicle particles of the DPPC and DSPC transiently increases near the interdigitation pressure, whereas the chemically induced interdigitation by adding ethanol to the DSPC bilayer membrane under atmospheric pressure produce no such change in the particle size. Taking account of the critical packing parameter of the PC molecule, the above experimental results would lead us to the conclusion that the pressure-induced interdigitation is attributable to the increase in repulsive interaction between the polar head groups of the PC molecules resulting from the orientational change of the head group from a parallel alignment to a perpendicular one with respect to the bilayer surface by applying pressure, namely the transient state: it occurs when the repulsive interaction exceeds a threshold value for the balance between the repulsive interaction and the attractive interaction among the hydrophobic acyl chains.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 8","pages":"Article 184385"},"PeriodicalIF":2.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340432","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":"Alamethicin channel inactivation caused by voltage-driven flux of alamethicin","authors":"Joshua J. Maraj,&nbsp;Jessie D. Ringley,&nbsp;Stephen A. Sarles","doi":"10.1016/j.bbamem.2024.184386","DOIUrl":"10.1016/j.bbamem.2024.184386","url":null,"abstract":"<div><div>We show that voltage alone can inactivate alamethicin channels, which has been previously observed for monazomycin and suzukacillin channels. The voltage required to trigger inactivation is above the potential to form channels, and, like with channel activation, this threshold reduces with increasing peptide concentration and membrane fluidity. Since similar monazomycin channels inactivate via channel break up and translocation, we hypothesized that inactivation of alamethicin channels occurs via the same mechanism. Our data prove this hypothesis to be true through two experiments. First, we show that inactivation of channels at positive voltages when peptides are supplied to only the <em>cis</em> side correlates to new channel activity on the <em>trans</em> side at negative potentials. This result indicates translocation of alamethicin peptides occurs only during voltage-induced inactivation. Second, we measured the ratio of steady-state (with inactivation) to ideal (without inactivation) conductance versus voltage for membranes with equal amounts of alamethicin on both sides and used these values to quantify alamethicin flux. Plotting flux versus steady-state conductance across multiple alamethicin concentrations shows a single linear dependence, signifying that translocated peptides originate from active channels that break up under prolonged voltage. Given the frequent use of alamethicin as model ion channels, these results add important understanding of their kinetic responses when subjected to prolonged, high voltages.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 8","pages":"Article 184386"},"PeriodicalIF":2.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340433","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":"Benzohydroxamate and nitrobenzohydroxamate affect membrane order: Correlations between spectroscopic and molecular dynamics to approach tuberculosis","authors":"Lucas Thadeu Felipe Kokuszi ,&nbsp;Yago Mendes Paes ,&nbsp;Aline Loise Santana Faria ,&nbsp;Jesus Alvarado-Huayhuaz ,&nbsp;Maurício Dornelles Caldeira Balboni ,&nbsp;Marinalva Cardoso dos Santos ,&nbsp;Sandra Cruz dos Santos ,&nbsp;Juliano Rosa de Menezes Vicenti ,&nbsp;Alexandre Luis Parize ,&nbsp;Adriano Velasque Werhli ,&nbsp;Karina dos Santos Machado ,&nbsp;Vânia Rodrigues de Lima","doi":"10.1016/j.bbamem.2024.184378","DOIUrl":"10.1016/j.bbamem.2024.184378","url":null,"abstract":"<div><p>This work correlates the effects of benzohydroxamate (BH) and nitrobenzohydroxamate (NBH) anions in two membrane models which may be used for anti-tuberculosis (anti-TB) spectroscopic studies and/or computational studies. Firstly, the BH and NBH influence in the physico-chemical properties of soy asolectin (ASO)-based large multilamellar vesicles (MLVs) were evaluated by spectroscopic and calorimetric studies. In parallel, the BH and NBH interaction with a <em>Mycobacterium tuberculosis</em> (Mtb) inner membrane model, composed of phosphatidyl-myo-inositol-dimannoside (PIM₂), was investigated by molecular dynamics (MD) simulations. Spectroscopic data showed a localization of BH close to the lipid phosphate group, while NBH was found close to the choline region. The BH ordered the ASO choline, phosphate and carbonyl regions and disrupted the acyl methylenes, reducing the membrane packing of the lipid hydrophobic region. On the other hand, NBH showed an ordering effect in all the lipid groups (polar, interface and hydrophobic ones). By MD studies, it was found that NBH enhanced the stability of the PIM₂ membrane more than BH, while also being positioned closer to its mannosyl oxygens. As in ASO MLVs, BH was localized close to the PIM₂ phosphate group and disrupted its acyl chains. However, higher values of lateral diffusion were observed for NBH than BH. Despite this, BH and NBH increased the membrane thickness by 35 %, which suggests a global ordering effect of both drugs. Findings of this work reinforce the accordance and complementarity between MLVs based on ASO and the PIM₂ MD model results to study the drug effects in Mtb membrane properties.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 8","pages":"Article 184378"},"PeriodicalIF":2.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008217","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":"Foam fractionation studies of recombinant human apolipoprotein A-I","authors":"Kyle Lethcoe ,&nbsp;Colin A. Fox ,&nbsp;Anouar Hafiane ,&nbsp;Robert S. Kiss ,&nbsp;Jianfang Liu ,&nbsp;Gang Ren ,&nbsp;Robert O. Ryan","doi":"10.1016/j.bbamem.2024.184375","DOIUrl":"10.1016/j.bbamem.2024.184375","url":null,"abstract":"<div><p>Apolipoprotein A-I (apoA-I), the primary protein component of plasma high-density lipoproteins (HDL), is comprised of two structural regions, an N-terminal amphipathic α-helix bundle domain (residues 1–184) and a hydrophobic C-terminal domain (residues 185–243). When a recombinant fusion protein construct [bacterial pelB leader sequence – human apoA-I (1–243)] was expressed in <em>Escherichia coli</em> shaker flask cultures, apoA-I was recovered in the cell lysate. By contrast, when the C-terminal domain was deleted from the construct, large amounts of the truncated protein, apoA-I (1–184), were recovered in the culture medium. Consequently, following pelB leader sequence cleavage in the <em>E. coli</em> periplasmic space, apoA-I (1–184) was secreted from the bacteria. When the pelB-apoA-I (1–184) fusion construct was expressed in a 5 L bioreactor, substantial foam production (~30 L) occurred. Upon foam collection and collapse into a liquid foamate, SDS-PAGE revealed that apoA-I (1–184) was the sole major protein present. Incubation of apoA-I (1–184) with phospholipid vesicles yielded reconstituted HDL (rHDL) particles that were similar in size and cholesterol efflux capacity to those generated with full-length apoA-I. Mass spectrometry analysis confirmed that pelB leader sequence cleavage occurred and that foam fractionation did not result in unwanted protein modifications. The facile nature and scalability of bioreactor-based apolipoprotein foam fractionation provide a novel means to generate a versatile rHDL scaffold protein.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184375"},"PeriodicalIF":2.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916050","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":"Nanoscale lipid domains determine the dynamic molecular portraits of mixed DOPC/DOPS bilayers in a fluid phase: A computational insight","authors":"Irina I. Veretenenko ,&nbsp;Yury A. Trofimov ,&nbsp;Nikolay A. Krylov ,&nbsp;Roman G. Efremov","doi":"10.1016/j.bbamem.2024.184376","DOIUrl":"10.1016/j.bbamem.2024.184376","url":null,"abstract":"<div><p>Lateral heterogeneity, or mosaicity, is a fundamental property inherent to cell membranes that is crucial for their functioning. While microscopic inhomogeneities (e.g. rafts) are easily detected experimentally, lipid domains with nanoscale dimensions (nanoclusters of nanodomains, NDs) resist reliable characterization by instrumental methods. In such a case, important insight can be gained via computer modeling. Here, NDs composed of lipid's head groups in the mixed zwitterionic dioleoylphosphatidylcholine (DOPC) and negatively charged dioleoylphosphatidylserine (DOPS) bilayers were studied by molecular dynamics. A new algorithm has been developed to identify NDs. Unlike most similar methods, it implicitly considers the heterogeneous distribution of lipid head atomic density and does not require subjectively chosen parameters. In DOPS-rich membranes, lipids form more compact and stable NDs due to strong interlipid interactions. In DOPC-rich systems, NDs arise due to the “packing” effect of weakly bound lipid heads. The clustering picture is related to the physical properties of the bilayer surface: DOPS-rich systems show more pronounced surface heterogeneity of hydrophilic/hydrophobic regions compared to DOPC-rich ones. The results obtained are important for the effective quantitative characterization of the “dynamic molecular portrait” of a membrane surface – its “fingerprint” characterizing dynamical distribution of its physicochemical properties.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184376"},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900844","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":"Dynamic protein-protein interactions of KCNQ1 and KCNE1 measured by EPR line shape analysis","authors":"Rebecca B. Stowe ,&nbsp;Alison Bates ,&nbsp;Lauryn E. Cook ,&nbsp;Gunjan Dixit ,&nbsp;Indra D. Sahu ,&nbsp;Carole Dabney-Smith ,&nbsp;Gary A. Lorigan","doi":"10.1016/j.bbamem.2024.184377","DOIUrl":"10.1016/j.bbamem.2024.184377","url":null,"abstract":"<div><p>KCNQ1, also known as Kv7.1, is a voltage gated potassium channel that associates with the KCNE protein family. Mutations in this protein has been found to cause a variety of diseases including Long QT syndrome, a type of cardiac arrhythmia where the QT interval observed on an electrocardiogram is longer than normal. This condition is often aggravated during strenuous exercise and can cause fainting spells or sudden death. KCNE1 is an ancillary protein that interacts with KCNQ1 in the membrane at varying molar ratios. This interaction allows for the flow of potassium ions to be modulated to facilitate repolarization of the heart. The interaction between these two proteins has been studied previously with cysteine crosslinking and electrophysiology. In this study, electron paramagnetic resonance (EPR) spectroscopy line shape analysis in tandem with site directed spin labeling (SDSL) was used to observe changes in side chain dynamics as KCNE1 interacts with KCNQ1. KCNE1 was labeled at different sites that were found to interact with KCNQ1 based on previous literature, along with sites outside of that range as a control. Once labeled KCNE1 was incorporated into vesicles, KCNQ1 (helices S1-S6) was titrated into the vesicles. The line shape differences observed upon addition of KCNQ1 are indicative of an interaction between the two proteins. This method provides a first look at the interactions between KCNE1 and KCNQ1 from a dynamics perspective using the full transmembrane portion of KCNQ1.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184377"},"PeriodicalIF":2.8,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892789","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":"Influence of archaeal lipids isolated from Aeropyrum pernix K1 on physicochemical properties of sphingomyelin-cholesterol liposomes","authors":"Jan Kejžar ,&nbsp;Polona Mrak ,&nbsp;Ilja Gasan Osojnik Črnivec ,&nbsp;Nataša Poklar Ulrih","doi":"10.1016/j.bbamem.2024.184374","DOIUrl":"10.1016/j.bbamem.2024.184374","url":null,"abstract":"<div><p>We investigated the influence of archaeal lipids (C_25,25) isolated from thermophilic archaeon <em>Aeropyrum pernix</em> K1 on physicochemical properties of liposomes comprised of egg sphingomyelin (SM) and cholesterol (CH) using fluorescence emission anisotropy, calcein release studies, dynamic light scattering, transmission electron microscopy and phase analysis light scattering. The 2 mol% addition of archaeal lipids enabled formation of small unilamellar vesicles by sonication while also having significant effect on reducing mean size, polydispersity index and zeta potential of C_25,25/SM/CH vesicles. Increasing the ratio of C_25,25 lipids in mixture of C_25,25/SM/CH decreased lipid ordering parameter in dose dependent manner at different temperatures. We also demonstrated that adding 15 mol% C_25,25 to SM/CH mixture will cause it to notably interact with fetal bovine serum which could make them a viable alternative adjuvant to synthetic ether-linked lipids in development of advanced liposomal vaccine delivery systems. The prospect of combining the proven strengths of SM/CH mixtures with the unique properties of C_25,25 opens exciting possibilities for advancing drug delivery technologies, promising to yield formulations that are both highly effective and adaptable to a range of therapeutic applications.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184374"},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0005273624001056/pdfft?md5=afd73738d180040195ca0dedcd675148&pid=1-s2.0-S0005273624001056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756814","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}

{"title":"Lipid composition affects the thermal stability of cytochrome P450 3A4 in nanodiscs","authors":"Tim G.J. Knetsch,&nbsp;Marcellus Ubbink","doi":"10.1016/j.bbamem.2024.184372","DOIUrl":"10.1016/j.bbamem.2024.184372","url":null,"abstract":"<div><p>Nanodiscs (NDs), self-assembled lipid bilayers encircled by membrane scaffold proteins (MSPs), offer a versatile platform for the reconstitution of membrane proteins for structural and biochemical investigations. Saturated, isoprenoid lipids are commonly found in thermophiles and have been associated with thermotolerance. To test whether these lipids confer additional stability on ND-incorporated membrane proteins, this study focuses on the thermal stability of human cytochrome P450 3A4 (CYP3A4) inside NDs composed of different phosphocholine lipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). NDs were characterized using size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) and densitometric SDS-PAGE. CYP3A4-DPhPC-NDs were found to comprise three MSP copies instead of the canonical dimer, as reported before for the empty NDs. Rapid, thermally induced unfolding of CYP3A4 inside NDs measured using circular dichroism and differential scanning fluorimetry (nanoDSF) revealed that the CYP3A4 melting temperature was dependent on ND composition. In POPC and DMPC-CYP3A4-NDs the melting temperature was comparable to CYP3A4 without NDs (59 °C). CYP3A4 in DPhPC-NDs showed an increase in melting temperature of 4 °C. Decline in CYP3A4 integrity as well as ND aggregation and disintegration occur at similar rates for all membrane types when subjected to exposure at 37 °C for several hours. The POPC and DMPC- CYP3A4-NDs show significant lipid loss over time, which is not observed for DPhPC-NDs. The results demonstrate that thermally induced denaturation of protein-NDs is a complex, multifaceted process, which is not represented well by rapid thermal unfolding experiments.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184372"},"PeriodicalIF":2.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0005273624001032/pdfft?md5=1cb18708a6c65e795da8bb046d83b80f&pid=1-s2.0-S0005273624001032-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756815","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}

{"title":"The impact of transmembrane peptides on lipid bilayer structure and mechanics: A study of the transmembrane domain of the influenza A virus M2 protein","authors":"Yasith Indigahawela Gamage,&nbsp;Yasinthara Wadumesthri,&nbsp;Humberto Rodríguez Gutiérrez,&nbsp;Dmitri V. Voronine,&nbsp;Jianjun Pan","doi":"10.1016/j.bbamem.2024.184373","DOIUrl":"10.1016/j.bbamem.2024.184373","url":null,"abstract":"<div><p>Transmembrane peptides play important roles in many biological processes by interacting with lipid membranes. This study investigates how the transmembrane domain of the influenza A virus M2 protein, M2TM, affects the structure and mechanics of model lipid bilayers. Atomic force microscopy (AFM) imaging revealed small decreases in bilayer thickness with increasing peptide concentrations. AFM-based force spectroscopy experiments complemented by theoretical model analysis demonstrated significant decreases in bilayer's Young's modulus (E) and lateral area compressibility modulus (K_A). This suggests that M2TM disrupts the cohesive interactions between neighboring lipid molecules, leading to a decrease in both the bilayer's resistance to indentation (E) and its ability to resist lateral compression/expansion (K_A). The large decreases in bilayer elastic parameters (i.e., E and K_A) contrast with small changes in bilayer thickness, implying that bilayer mechanics are not solely dictated by bilayer thickness in the presence of transmembrane peptides. The observed significant reduction in bilayer mechanical properties suggests a softening effect on the bilayer, potentially facilitating membrane curvature generation, a crucial step for M2-mediated viral budding. In parallel, our Raman spectroscopy revealed small but statistically significant changes in hydrocarbon chain vibrational dynamics, indicative of minor disordering in lipid chain conformation. Our findings provide useful insights into the complex interplay between transmembrane peptides and lipid bilayers, highlighting the significance of peptide-lipid interactions in modulating membrane structure, mechanics, and molecular dynamics.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184373"},"PeriodicalIF":2.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756896","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":"Novel lipid-interaction motifs within the C-terminal domain of Septin10 from Schistosoma mansoni","authors":"Italo A. Cavini ,&nbsp;Marina G. Fontes ,&nbsp;Ana Eliza Zeraik ,&nbsp;Jose L.S. Lopes ,&nbsp;Ana Paula U. Araujo","doi":"10.1016/j.bbamem.2024.184371","DOIUrl":"10.1016/j.bbamem.2024.184371","url":null,"abstract":"<div><p>Septins are cytoskeletal proteins and their interaction with membranes is crucial for their role in various cellular processes. Septins have polybasic regions (PB1 and PB2) which are important for lipid interaction. Earlier, we and others have highlighted the role of the septin C-terminal domain (CTD) to membrane interaction. However, detailed information on residues/group of residues important for such feature is lacking. In this study, we investigate the lipid-binding profile of <em>Schistosoma mansoni</em> Septin10 (<em>Sm</em>SEPT10) using PIP strip and Langmuir monolayer adsorption assays. Our findings highlight the CTD as the primary domain responsible for lipid interaction in <em>Sm</em>SEPT10, showing binding to phosphatidylinositol phosphates. <em>Sm</em>SEPT10 CTD contains a conserved polybasic region (PB3) present in both animals and fungi septins, and a Lys (K367) within its putative amphipathic helix (AH) that we demonstrate as important for lipid binding. PB3 deletion or mutation of this Lys (K367A) strongly impairs lipid interaction. Remarkably, we observe that the AH within a construct lacking the final 43 amino acid residues is insufficient for lipid binding. Furthermore, we investigate the homocomplex formed by <em>Sm</em>SEPT10 CTD in solution by cross-linking experiments, CD spectroscopy, SEC-MALS and SEC-SAXS. Taken together, our studies define the lipid-binding region in <em>Sm</em>SEPT10 and offer insights into the molecular basis of septin-membrane binding. This information is particularly relevant for less-studied non-human septins, such as <em>Sm</em>SEPT10.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184371"},"PeriodicalIF":2.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695694","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}