Biochimica et biophysica acta. Biomembranes最新文献

Molecular dynamics study of SP-B fragment interactions with model lung surfactant bilayers. SP-B片段与肺表面活性物质双层相互作用的分子动力学研究。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-05-05 DOI: 10.1016/j.bbamem.2026.184537

Vahid Sheigani, Abinu Jyothini, Yimiao Zhao, Michael R Morrow, Ivan Saika-Voivod

{"title":"Molecular dynamics study of SP-B fragment interactions with model lung surfactant bilayers.","authors":"Vahid Sheigani, Abinu Jyothini, Yimiao Zhao, Michael R Morrow, Ivan Saika-Voivod","doi":"10.1016/j.bbamem.2026.184537","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184537","url":null,"abstract":"<p><p>Respiration depends on a lung surfactant layer to facilitate changes in surface area at the air-water interface. The 79-amino acid lung surfactant protein SP-B, normally present in dimer form, is essential to the functioning of lung surfactant. One important aspect of lung surfactant function is the recruitment and cycling of surfactant material to and from bilayer reservoirs. Full utilization of surfactant material available in multilamellar reservoirs presumably requires the formation of contacts between adjacent bilayer surfaces and the formation of connections between leaflets of a given surfactant bilayer. Some fragments of SP-B, including the N-terminal segment SP-B<sub>1-25</sub>, mimic the effects of full SP-B on model surfactant monolayers and in preparations applied in surfactant-deficient animal model studies. In this work, all-atom molecular dynamics simulations have been carried out on DPPC/POPG model bilayers containing multiple copies of SP-B<sub>1-25</sub> initially oriented along the bilayer surface, across the bilayer, or randomly as well as on model bilayers containing SP-B<sub>1-9</sub> randomly oriented on the bilayer surfaces. These results show that, over the microsecond durations of the simulations, SP-B<sub>1-25</sub> remains largely helical and can be accommodated along the bilayer surface, where it would be available to interact with adjacent bilayers, or across the bilayer which results in local perturbation of the bilayer surface. These observations provide some insight into the possible capacity of the N-terminal segment of SP-B to mediate both interbilayer and intrabilayer interactions that are presumably involved in the lipid assembly reorganization necessary to facilitate surfacant recruitment and recycling from bilayer reservoirs.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184537"},"PeriodicalIF":2.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832938","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}

引用次数: 0

Phase coexistence in multilayer phospholipid films treated with certain cryoprotectants. 经某些冷冻保护剂处理的多层磷脂膜的相共存。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-05-01 DOI: 10.1016/j.bbamem.2026.184536

Yulia V Zaytseva, Konstantin A Okotrub, Nikolay V Surovtsev

{"title":"Phase coexistence in multilayer phospholipid films treated with certain cryoprotectants.","authors":"Yulia V Zaytseva, Konstantin A Okotrub, Nikolay V Surovtsev","doi":"10.1016/j.bbamem.2026.184536","DOIUrl":"10.1016/j.bbamem.2026.184536","url":null,"abstract":"<p><p>The interaction of cryoprotective agents (CPAs) with complex phospholipid bilayers, crucial for cryopreservation, remains understudied beyond single-component models. We applied Raman mapping to multilayer films of DOPC/DPPC-d62/Chol = 1/3/1 exposed to the vapor phase of dimethyl sulfoxide (DMSO), glycerol, propylene glycol (PG), ethylene glycol (EG), and their deuterated analogues. Raman data allowed us to evaluate the chemical content, conformational ordering of DPPC-d62, and the CPA incorporation into coexisting phases. It was found that under dry conditions, DMSO can extract Chol from the phospholipid film to form a co-crystalline phase. When added to water, DMSO caused dehydration of the film, making the chemical and conformational content of the coexisting phases similar to the dry film. Films treated with glycerol showed properties that are most similar to those of hydrated films. For EG, we found a decrease in the coexistence region in the phase diagram. PG further decreased the size of the region of phase coexistence and increased the conformational disorder of phospholipids. Finally, our data show that domains with conformationally disordered lipids contain more CPA than those with ordered ones. Overall, our research demonstrates that CPAs can significantly impact the organization and properties of complex phospholipid bilayers.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184536"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810405","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}

引用次数: 0

How receptor conformation depends on lipid nanodisc size: Adenosine A_2A receptor and implications for class-A GPCR proteins. 受体构象如何取决于脂质纳米盘大小：腺苷A2A受体及其对a类GPCR蛋白的影响。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-28 DOI: 10.1016/j.bbamem.2026.184535

Veera Hägg, Ilya Levental, Shreyas Kaptan, Ilpo Vattulainen

{"title":"How receptor conformation depends on lipid nanodisc size: Adenosine A<sub>2A</sub> receptor and implications for class-A GPCR proteins.","authors":"Veera Hägg, Ilya Levental, Shreyas Kaptan, Ilpo Vattulainen","doi":"10.1016/j.bbamem.2026.184535","DOIUrl":"10.1016/j.bbamem.2026.184535","url":null,"abstract":"<p><p>Nanodiscs have become an exceptionally valuable tool to explore membrane proteins in an environment resembling native membranes. However, it remains unclear how well the lipid nanodisc environment matches the conditions under which membrane proteins function in cells. The goal of this work is to use atomic-level simulations to compare the environments experienced by membrane proteins in nanodiscs and non-strained planar membranes of identical lipid composition. We focus on the adenosine A<sub>2A</sub> receptor, a member of the GPCR family, and investigate how nanodisc size affects receptor properties. We specifically study typical nanodiscs, which, together with the surrounding membrane scaffolding protein, are ∼11 nm in diameter. We show that even simple lipid compositions give rise to nanoscale disc structures that modulate receptor conformational states, in contrast to planar, non-strained membrane structures. Deep learning methods reveal that the conformational distribution of the A<sub>2A</sub> receptor is skewed towards active-like structures compared to the planar membrane environment. However, the tendency of nanodiscs to modulate the conformation of the receptor turns out to be size-dependent. A reassuring observation is that when the diameter of the nanodiscs reaches ∼19 nm, the receptor conformations settle into a distribution whose key features correspond to those of a non-strained planar bilayer. The results support the view that the membrane environment affects the conformational distribution of GPCRs within them, and when it comes to the use of lipid nanodiscs, potential unwanted effects can be minimized by favoring the largest nanodiscs.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184535"},"PeriodicalIF":2.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810226","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}

引用次数: 0

Acylation of the RTX toxin MbxA stimulates host membrane disruption through a specific interaction with cholesterol RTX毒素MbxA的酰化通过与胆固醇的特定相互作用刺激宿主膜破坏。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2025-11-27 DOI: 10.1016/j.bbamem.2025.184487

Feby Mariam Chacko , Sarah Michelle Ganz , Anne Pfitzer-Bilsing , Sebastian Hänsch , Philipp Westhoff , Stefanie Weidtkamp-Peters , Sander H.J. Smits , Marten Exterkate , Lutz Schmitt

{"title":"Acylation of the RTX toxin MbxA stimulates host membrane disruption through a specific interaction with cholesterol","authors":"Feby Mariam Chacko , Sarah Michelle Ganz , Anne Pfitzer-Bilsing , Sebastian Hänsch , Philipp Westhoff , Stefanie Weidtkamp-Peters , Sander H.J. Smits , Marten Exterkate , Lutz Schmitt","doi":"10.1016/j.bbamem.2025.184487","DOIUrl":"10.1016/j.bbamem.2025.184487","url":null,"abstract":"<div><div>RTX toxins (Repeat in ToXins) are pore-forming toxins secreted by gram-negative bacteria. They are known for their ability to disrupt host cell membranes, among which various human cells. The acylation of specific lysine residues in these toxins is crucial for their hemolytic activity, but the precise mechanisms underlying this enhancement remain unclear. By comparing the lytic activities of acylated MbxA and its non-acylated form, we explored the role of acylation in the pore-forming behavior of this RTX toxin. Our findings demonstrate that acylation specific interactions of MbxA with cholesterol promote membrane disruption, both <em>in vitro</em> and in living cells. More specifically, acylation is not necessary for initial membrane binding, but markedly enhances pore formation. Overall, our results provide detailed insights into the molecular determinants that regulate MbxA toxin activity. We highlight a complex interplay between lipid composition (sterols), acylation, and membrane disruption, thereby advancing our general understanding of RTX toxin pathogenesis.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184487"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628387","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}

引用次数: 0

Blood coagulation protein binds to Ca2+-induced phosphatidylserine nanodomains as revealed by atomic force microscopy 凝血蛋白结合到Ca2+诱导的磷脂酰丝氨酸纳米结构域的原子力显微镜显示。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-17 DOI: 10.1016/j.bbamem.2026.184500

Jie Cheng , Junhong Lü , Xueling Li

{"title":"Blood coagulation protein binds to Ca2+-induced phosphatidylserine nanodomains as revealed by atomic force microscopy","authors":"Jie Cheng , Junhong Lü , Xueling Li","doi":"10.1016/j.bbamem.2026.184500","DOIUrl":"10.1016/j.bbamem.2026.184500","url":null,"abstract":"<div><div>The interaction between coagulation factor VIII (FVIII) and phospholipid membranes is a critical aspect of the blood clotting process. While it is known that FVIII binds to negatively charged phospholipids, the role of calcium ions (Ca<sup>2+</sup>) in this process remains an area of ongoing research. This study investigated the dynamic effects of Ca<sup>2+</sup> on FVIII binding to phospholipid membranes, in particular how Ca<sup>2+</sup>-induced nanodomain formation affects this interaction. Using in situ atomic force microscopy (AFM) imaging, we observed the morphological and structural changes of supported lipid bilayers (DPPC/DOPS and DOPC/DPPS systems) in response to Ca<sup>2+</sup>. The results showed that Ca<sup>2+</sup> not only alters the membrane lipid structure, but also promotes the formation of nanodomain in the phosphatidylserine (PS)-enriched regions. In the presence of Ca<sup>2+</sup>, FVIII bound preferentially to PS nanodomains with height differences of about 0.8 nm compared to adjacent membrane regions, and the binding process was further facilitated by Ca<sup>2+</sup>-induced reorganization of the lipid phases over time scales of 40–230 min. These findings provided new insights into the molecular mechanisms governing the interaction of FVIII with phospholipid membranes and underlined the crucial role of Ca<sup>2+</sup> in supporting the functional activity of coagulation protein.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184500"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002972","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}

引用次数: 0

Reverse micelles produce hydroxyapatite nanoparticles as more efficient gene delivery carriers than regular micelles 反向胶束产生的羟基磷灰石纳米颗粒作为比常规胶束更有效的基因传递载体。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bbamem.2026.184506

Vuk Uskoković

{"title":"Reverse micelles produce hydroxyapatite nanoparticles as more efficient gene delivery carriers than regular micelles","authors":"Vuk Uskoković","doi":"10.1016/j.bbamem.2026.184506","DOIUrl":"10.1016/j.bbamem.2026.184506","url":null,"abstract":"<div><div>Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles compared to regular ones. Similarly, water within reverse micelles exhibited more homogeneity and unexpected freedom, creating favorable entropic conditions for chemical reactions. CTAB showed strong electrostatic affinity for DNA and bound more effectively to HAp synthesized within the confined nanoscale environment of reverse micelles than to HAp produced in the aqueous continuum surrounding regular micelles. Also, reverse micelles produced narrowly dispersed, rod-shaped HAp nanoparticles, unlike the larger, macroporous particles formed in regular micelles. Both of these effects predisposed HAp from reverse micelles to exhibit a higher transfection efficiency in K7M2 osteosarcoma cells than its regular micelle counterpart. Despite these positive outcomes, HAp could only partially mitigate the cytotoxic effects of CTAB. Therefore, further exploration of advanced synthesis methods, biocompatible surfactants or strategies to preserve the synergy between HAp, CTAB and DNA while reducing CTAB toxicity is essential for enhancing the gene delivery performance of reverse micellar HAp.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184506"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043557","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}

引用次数: 0

Effect of ice recrystallization inhibition on hydrogen bonding interactions and membrane leakage of liposomes 冰重结晶抑制对脂质体氢键相互作用和膜渗漏的影响。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bbamem.2026.184502

Dejia Liu , Harriëtte Oldenhof , Harald Sieme , Willem F. Wolkers

{"title":"Effect of ice recrystallization inhibition on hydrogen bonding interactions and membrane leakage of liposomes","authors":"Dejia Liu , Harriëtte Oldenhof , Harald Sieme , Willem F. Wolkers","doi":"10.1016/j.bbamem.2026.184502","DOIUrl":"10.1016/j.bbamem.2026.184502","url":null,"abstract":"<div><div>In this study, effects of ice recrystallization on membrane stability of liposomes were investigated using liposomes encapsulating a fluorescent dye. Membrane leakage was studied after freezing and storage at varying temperatures in solutions supplemented with polyvinyl alcohol (PVA), polyethylene glycol (PEG), dimethyl sulfoxide (DMSO) and combinations thereof. Leakage studies were corroborated with studies on ice crystal growth and hydrogen bonding interactions during holding at temperatures just below the ice melting temperature, i.e., at −10 °C. Cryomicroscopic observations confirmed that PVA exhibits ice recrystallization inhibition activity, whereas PEG did not. Both PVA and PEG reduced freezing-induced liposome leakage, alone and in combination with low DMSO concentrations. Temperature-scanning infrared spectroscopy (FTIR) combined with principal component analysis (PCA) was used as a novel approach to probe differences in hydrogen bonding interactions between frozen buffered saline (PBS) containing PVA and PEG. Score and loading plots show that symmetric hydrogen bonds are predominant with addition of PVA, and that the cluster of principal component data points remain compact during holding under ice recrystallization conditions. By contrast, PBS supplemented with PEG and PBS control solutions are characterized by weak hydrogen bonding interactions and more disperse clusters of principal component data points denoting rearrangements in hydrogen bonding interactions associated with ice crystal growth during holding. In conclusion, beneficial effects of adding PVA or PEG in cryopreservation solutions for liposomes are most evident under suboptimal cryopreservation conditions, e.g., during storage at elevated subzero temperatures, and when low concentrations of DMSO are used.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184502"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028343","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}

引用次数: 0

NMR structural analysis and peptidoglycan binding properties of the peptidoglycan associated lipoprotein (PAL) from Escherichia coli 大肠杆菌肽聚糖相关脂蛋白（PAL）的核磁共振结构分析及肽聚糖结合特性。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bbamem.2026.184501

Ishrat M. Jalal , Hiroaki Ishida , Hans J. Vogel

{"title":"NMR structural analysis and peptidoglycan binding properties of the peptidoglycan associated lipoprotein (PAL) from Escherichia coli","authors":"Ishrat M. Jalal , Hiroaki Ishida , Hans J. Vogel","doi":"10.1016/j.bbamem.2026.184501","DOIUrl":"10.1016/j.bbamem.2026.184501","url":null,"abstract":"<div><div>The peptidoglycan associated lipoprotein (Pal) is crucial in Gram-negative bacteria, participating in outer-membrane integrity and septal wall constriction during cell division. It is also implicated in pathogenesis by mediating sepsis and immune responses. Pal has been one of the most intensively studied vaccine targets and herein we report a structural characterization and functional analysis of <em>Escherichia coli</em> Pal (Ec.Pal), as a member of the peptidoglycan-binding protein (PGBP) family. Multidimensional solution NMR spectroscopy was employed to obtain backbone assignments for truncated and full-length constructs of Ec.Pal, revealing that these proteins adopt the characteristic secondary structure of the OmpA_C-like domain and that the core residues fold similarly to the crystal structure reported for a truncated protein (PDB <span><span>1OAP</span><svg><path></path></svg></span>). However, full-length Ec.Pal possesses a previously unobserved N-terminal α1-helix, which in conjunction with a 30-residue flexible N-terminal linker, distinguishes Ec.Pal from other PGBP members. Biophysical studies further demonstrated the role of this terminal region in mediating the dimerization of Ec.Pal, contrasting its behavior with other PGBPs. Moreover, our findings for an acylated version of Ec.Pal which was purified as a SMALP-complex, suggest that Ec.Pal can interact with membrane mimetics through the flexible N-terminal region as well. Additionally, the C-terminal domain of Ec.Pal was shown to bind peptidoglycan (PG) components and co-purify with the PG-precursor (PGp), highlighting its role in cell wall dynamics. These results contribute to understanding the structural basis of Ec.Pal's function in bacterial membrane biology and its potential as a therapeutic target.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184501"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028296","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}

引用次数: 0

Biophysical approaches to antimicrobial peptide–membrane characterization 抗菌肽膜表征的生物物理方法。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI: 10.1016/j.bbamem.2026.184499

A. Roldán , P. Fernández-García , V. Lladó , M. Torres , P.V. Escribá , M. Salvador-Castell

{"title":"Biophysical approaches to antimicrobial peptide–membrane characterization","authors":"A. Roldán , P. Fernández-García , V. Lladó , M. Torres , P.V. Escribá , M. Salvador-Castell","doi":"10.1016/j.bbamem.2026.184499","DOIUrl":"10.1016/j.bbamem.2026.184499","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) represent a current strategy to develop new antibiotics against multi-resistant pathogens. The potential antibiotic activity of AMPs is related to their amphipathic properties and the presence of positively charged residues, which may interact with the negatively charged bacterial membranes. In contrast, they exhibit lower interaction with the eukaryotic, neutrally charged membranes. This is the primary reason AMPs can distinguish between eukaryotic and prokaryotic membranes.</div><div>AMPs are usually modified or designed <em><strong>de novo</strong></em>, and their properties can be changed by inserting specific amino acid residues into their sequence. To assist in the rational design of AMPs, it is helpful to explore the biophysical changes they may induce in target cell membranes. Therefore, bacterial and eukaryotic model lipid membranes have been extensively used for this purpose. Parameters such as selective binding, lipid membrane interactions, membrane packing, permeability, hydration, and restructuring facilitate the exploration of peptide regions of interest. These parameters can be studied using various physicochemical techniques, including differential scanning calorimetry, X-ray diffraction, nuclear magnetic resonance, and fluorescence spectroscopy.</div><div>This review aims to provide a practical guide to the main biophysical techniques used to explore the potential antibiotic activity of AMPs using model membranes, and to examine lipid-peptide interactions in order to define the mechanisms of action of these antimicrobial peptides. These techniques determine whether the peptide interacts specifically with bacterial membranes, the preferred bacterial target of a given AMP, the binding affinities of AMPs, potential pore formation and its geometry, and the impact of these interactions on both bacterial and eukaryotic membranes.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184499"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987895","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}

引用次数: 0

Investigating the electrostatics underlying activation of the β 2 adrenergic receptor 研究β 2肾上腺素能受体激活的静电

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.bbamem.2026.184503

Julia M. Montgomery , Justin A. Lemkul

{"title":"Investigating the electrostatics underlying activation of the β 2 adrenergic receptor","authors":"Julia M. Montgomery , Justin A. Lemkul","doi":"10.1016/j.bbamem.2026.184503","DOIUrl":"10.1016/j.bbamem.2026.184503","url":null,"abstract":"<div><div>G-protein coupled receptors (GPCRs) are the largest family of membrane proteins in humans and represent critical targets for drug discovery efforts. Among GPCRs, the <span><math><mi>β</mi></math></span>-2 adrenergic receptor (<span><math><mi>β</mi></math></span> <sub>2</sub>AR) has served as a prototypical example of the protein family as well as an important target for pulmonary diseases. As such, much work has been done to investigate this GPCR experimentally and computationally. Many of the interactions that drive activation of <span><math><mi>β</mi></math></span> <sub>2</sub>AR are defined by electrostatics, emphasizing the need for robust simulations with accurate force field models. Only with recent advancements in computing capabilities and refined force fields has it become feasible to simulate this membrane protein on relevant time scales and with sufficiently accurate physical models. Here, we report outcomes of simulations with the Drude polarizable force field to explore the electrostatics underlying <span><math><mi>β</mi></math></span> <sub>2</sub>AR dynamics, marking the first application of explicit electronic polarization in this protein. We found that perturbation of intrinsic dipole moments in key microswitch residues associated with ligand binding is important for subtle conformational changes, resulting in different in conformational sampling compared to a nonpolarizable force field. The results of this study provide a new view of this common drug target with an emphasis on the role of electrostatics.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184503"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973004","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}

引用次数: 0