Biophysical chemistry最新文献_第2页

Structural basis of molecular recognition of pyridoxal 5′-phosphate in a bacterial periplasmic binding protein 细菌周围质结合蛋白中吡哆醛5′-磷酸分子识别的结构基础。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-26 DOI: 10.1016/j.bpc.2025.107547

Miriana Quaranta, Stefano Pascarella

Vitamin B₆ and its vitamers are essential in bacteria. Many are auxotrophic for B₆ vitamers and require salvage pathways and membrane uptake systems. Despite the importance of the uptake systems, very few transporters have been structurally characterized. The structure of the periplasmic binding protein (P5PA) of an ABC uptake transporter from the pathogen Actinobacillus pleuropneumoniae has been recently solved in complex with pyridoxal 5′-phosphate (PLP). Another close homolog from the same organism, AfuA, had been structurally characterized as a complex with glucose-6-phosphate (G6P). To study the molecular recognition of PLP by P5PA, a comparative approach has been applied. The heterologous complexes P5PA-G6P and AfuA-PLP have been generated by docking. Systematic molecular dynamics simulations have been applied to the native and heterologous complexes. Binding energies and molecular interactions have been compared for all the complexes. The results suggest the selective binding of the ligand is achieved by a combination of structural factors specific to each protein, including shape of the binding site, steric hindrance, hydrogen bonding, electrostatic and hydrophobic interactions. No single residue is uniquely responsible for ligand specificity although a few side chains play a significant role. Heterologous ligands are subject to destabilizing interactions that provoke the distortion of the ligand itself and the alteration of the protein dynamics. Residue Q267 appears to provide a significant stabilization contribution in the P5PA-PLP complex but not in AfuA-PLP. Likewise, D207 provides stabilization in the AfuA-G6P complex and not in AfuA-PLP. The indications obtained suggest strategies for the design of specific inhibitors.

维生素B6和它的维生素是细菌所必需的。许多是营养不良的维生素B6和需要补救途径和膜摄取系统。尽管摄取系统很重要，但很少有转运体被结构表征。病原体胸膜肺炎放线菌ABC摄取转运体的质周结合蛋白（P5PA）的结构最近与吡哆醛5'-磷酸（PLP）复合物一起解决。来自同一生物体的另一个密切同源物AfuA在结构上被表征为葡萄糖-6-磷酸（G6P）的复合物。为了研究P5PA对PLP的分子识别，我们采用了比较的方法。通过对接生成了异源配合物P5PA-G6P和AfuA-PLP。系统的分子动力学模拟已应用于天然和异种配合物。比较了所有配合物的结合能和分子相互作用。结果表明，配体的选择性结合是由每种蛋白质特异性结构因素的组合实现的，包括结合位点的形状、位阻、氢键、静电和疏水相互作用。虽然有几个侧链起着重要的作用，但没有一个残基是唯一负责配体特异性的。异源配体受到不稳定相互作用的影响，引起配体本身的扭曲和蛋白质动力学的改变。残基Q267似乎在P5PA-PLP复合体中提供了显著的稳定贡献，但在AfuA-PLP中没有。同样，D207对AfuA-G6P复合物起到稳定作用，而对AfuA-PLP不起作用。获得的适应症为设计特异性抑制剂提供了策略。

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引用次数: 0

Biophysical assessment of protein stability in ethanol-stressed environments via UV absorption and fluorescence spectroscopies 利用紫外吸收和荧光光谱对乙醇胁迫环境中蛋白质稳定性的生物物理评价

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-21 DOI: 10.1016/j.bpc.2025.107538

Erşed Akyüz , Mikhail M. Vorob'ev , Günnur Güler

Maintaining the structure and functionality of proteins is crucial in applications ranging from food preservation to pharmaceutical formulation. Ethanol, while commonly used as a solvent and preservative, can induce structural changes in proteins depending on its concentration and the specific structure of the protein itself. This study investigates the structural effects of ethanol on three types of model proteins, namely bovine serum albumin (BSA), β-Lactoglobulin (β-Lg), and β-Casein (β-Cn), by using UV–Vis spectroscopy and fluorescence spectroscopy. The conformational responses of proteins in water-EtOH solutions of various ethanol concentrations (0–10 %, v/v) were analyzed through absorbance and emission spectral changes. At increasing ethanol concentration, UV absorption data showed distinct protein-dependent spectral changes. β-Lg and β-Cn exhibited strong hypochromism (an absorbance decrease of ∼25 %) and red-shifting at 222 nm and 220 nm, respectively, indicating partial unfolding and solvent exposure of aromatic residues. BSA demonstrated subtle changes, and consistent quenching in fluorescence with a continuous blue-shifting to 330 nm, suggesting a moderate overall stability and local rearrangements in its structure. β-Cn exhibited red-shifted fluorescence and quenching, reflecting its flexible, disordered structure and heterogeneous response to solvent conditions. Statistical analysis revealed that while fluorescence spectroscopy was highly sensitive to the intrinsic differences between proteins (p < 0.001), the ethanol-induced conformational changes were too subtle to be detected as a statistically significant treatment effect. The consistency of these trends indicates a rational underlying mechanism of interaction. This reflects the subtle nature of the effect at the tested concentrations rather than the absence of an effect. Moreover, these results unveil the protein-specific effects of ethanol and strongly emphasize the importance of solvent composition in maintaining protein integrity. Ethanol concentrations up to 5 % may offer protein stability whereas high ethanol levels (≥ 5–10 %) promote structural perturbations. These results will be useful for both basic scientific research, such as biophysical studies and the advancement of optical techniques, and various industrial uses.

维持蛋白质的结构和功能在从食品保存到药物配方的应用中至关重要。乙醇虽然通常用作溶剂和防腐剂，但它可以根据其浓度和蛋白质本身的特定结构引起蛋白质的结构变化。本研究采用紫外可见光谱和荧光光谱技术研究了乙醇对牛血清白蛋白（BSA）、β-乳球蛋白（β-Lg）和β-酪蛋白（β-Cn）三种模型蛋白的结构影响。通过吸收光谱和发射光谱的变化，分析了蛋白质在不同乙醇浓度（0 - 10%,v/v）水溶液中的构象响应。随着乙醇浓度的增加，紫外吸收数据显示出明显的蛋白质依赖性光谱变化。β-Lg和β-Cn分别在222 nm和220 nm处表现出强烈的低色性（吸光度下降约25%）和红移，表明芳香残基部分展开和溶剂暴露。BSA表现出微妙的变化，荧光持续猝灭，连续蓝移至330 nm，表明其整体稳定性中等，结构局部重排。β-Cn表现出红移荧光和猝灭，反映了其柔性、无序结构和对溶剂条件的非均相响应。统计分析显示，虽然荧光光谱对蛋白质之间的内在差异非常敏感（p < 0.001），但乙醇引起的构象变化太微妙，无法作为统计学上显着的治疗效果进行检测。这些趋势的一致性表明了一种合理的潜在相互作用机制。这反映了在测试浓度下影响的微妙性质，而不是没有影响。此外，这些结果揭示了乙醇对蛋白质的特异性作用，并强调了溶剂成分在维持蛋白质完整性方面的重要性。高达5%的乙醇浓度可以提供蛋白质稳定性，而高乙醇水平（≥5 - 10%）会促进结构扰动。这些结果将有助于基础科学研究，如生物物理学研究和光学技术的进步，以及各种工业用途。

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引用次数: 0

Cationic carboxymethyl chitosan nanofibers embedded with silver nanoparticles for enhanced antibacterial applications 嵌入银纳米粒子的阳离子羧甲基壳聚糖纳米纤维增强抗菌应用。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-14 DOI: 10.1016/j.bpc.2025.107537

Neha Devi , Satish Kumar Pandey , Nishima Wangoo

There has been a growing concern regarding antibiotic resistance which has led to the design of new antibacterial nanocomposite with high efficiency and low cytotoxicity. This report demonstrates an approach for the design of a nanocomposite comprising of histidine tagged silver nanoparticles (His@AgNPs) embedded it in a carboxymethyl chitosan hydrogel (CHG). Carboxymethyl chitosan was used as a cationic polymer substrate to reinforce the antibacterial activity of the embedded silver nanoparticles. ICP-MS showed sufficient release of silver ions which results in enhanced antibacterial activity. In addition, the hydrogel with embedded silver nanoparticles exhibited excellent antibacterial performance against gram-negative Escherichia coli and gram-positive Staphylococcus aureus through a “kill-release” stratagem, which was mainly due to the synergistic effect of CHG and Ag⁺ ions release. The results showed that the cross-linking may enhance antibacterial activities of nanocomposite (CHG-His@AgNPs) by approximately 4-folds in comparison to His@AgNPs. A strong signal observed in confocal microscopy confirmed the successful internalization of the nanocomposite in tested microorganisms. The change in the morphology of the bacterial cells upon the treatment with nanocomposite was observed through FE-SEM microscopy which confirmed the antibacterial activity of the nanocomposite. The synthesized nanocomposite can thereby serve as an excellent candidate for tackling antibiotic resistance.

人们对抗生素耐药性的关注日益增加，这促使人们设计出高效率、低细胞毒性的新型抗菌纳米复合材料。本报告演示了一种设计纳米复合材料的方法，该纳米复合材料包括将组氨酸标记的银纳米颗粒（His@AgNPs）嵌入羧甲基壳聚糖水凝胶（CHG）中。采用羧甲基壳聚糖作为阳离子聚合物底物，增强银纳米粒子的抗菌活性。ICP-MS显示银离子释放充分，抗菌活性增强。此外，包埋银纳米颗粒的水凝胶对革兰氏阴性大肠杆菌和革兰氏阳性金黄色葡萄球菌表现出优异的抗菌性能，其“杀伤-释放”策略主要是由于CHG和Ag+离子释放的协同作用。结果表明，交联可使纳米复合材料（CHG-His@AgNPs）的抗菌活性比His@AgNPs提高约4倍。在共聚焦显微镜下观察到的强信号证实了纳米复合材料在被测微生物中的成功内化。通过FE-SEM观察了纳米复合材料处理后细菌细胞形态的变化，证实了纳米复合材料的抗菌活性。因此，合成的纳米复合材料可以作为解决抗生素耐药性的极好候选材料。

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引用次数: 0

Probing the cytotoxicity and the dynamic interaction of IIKK cationic peptides with human melanoma cells 探索IIKK阳离子肽与人类黑色素瘤细胞的细胞毒性和动态相互作用。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-11 DOI: 10.1016/j.bpc.2025.107536

Luciana Marciano Sergio , Amanda Sansone Semerdjian , Manoel Arcisio-Miranda

Cationic peptides have emerged as promising candidates in anticancer therapy due to their ability to directly target the plasma membrane of cancer cells, a mechanism that could potentially bypass traditional drug resistance pathways. In this study, we evaluated the cytotoxic activity and cell-membrane binding properties of three amphiphilic cationic peptides from the G(IIKK)ₙI-NH₂ family (n = 2–4) against human melanoma cells (SK-MEL-28). By performing MTT assays and tracking the propidium iodide (PI) uptake throughout peptide-cell interaction, we evaluated peptides' cytotoxicity. Assessment of the interaction dynamics was conducted by fluorescence spectroscopy assays with FPE, a surface potential sensitive probe. This evaluation indicated that an increase in net positive charge was relatable to a lower dissociation constant (K_d). Notably, G(IIKK)₄I-NH₂ showed the highest cytotoxicity, significant morphological alterations, rapid membrane permeabilization, and the lowest K_d, indicating a stronger membrane affinity when compared to the other peptides. G(IIKK)₃I-NH₂, in the same manner as G(IIKK)₄I-NH₂, revealed a cooperative binding behavior, evidenced by a Hill coefficient > 1. An inverse correlation between peptide-cell membrane dissociation constants and cytotoxicity was established, supporting the notion that membrane interaction is a critical determinant of anticancer activity. In addition, we used a cell surface membrane potential probe to possibly anticipate the in vitro activity of cationic peptides. Altogether, these findings provide mechanistic insights into peptide-cell membrane interactions and may offer a basis for the rational design of novel anticancer peptides targeting melanoma.

由于阳离子肽能够直接靶向癌细胞的质膜，这种机制可能绕过传统的耐药途径，因此在抗癌治疗中成为有希望的候选者。在这项研究中，我们评估了来自G（IIKK）的三种两亲性阳离子肽（n = 2-4）对人类黑色素瘤细胞（SK-MEL-28）的细胞毒活性和细胞膜结合特性。通过MTT测定和跟踪肽-细胞相互作用过程中碘化丙啶（PI）的摄取，我们评估了肽的细胞毒性。用FPE（一种表面电位敏感探针）荧光光谱分析相互作用动力学。这一评价表明，净正电荷的增加与较低的解离常数（Kd）有关。值得注意的是，G（IIKK）₄i - nh2表现出最高的细胞毒性、显著的形态改变、快速的膜通透性和最低的Kd，表明与其他肽相比具有更强的膜亲和性。G(IIKK) 3i - nh2与G（IIKK）₄i - nh2表现出协同结合行为，希尔系数bbb1证明了这一点。肽-细胞膜解离常数与细胞毒性之间存在负相关关系，支持细胞膜相互作用是抗癌活性关键决定因素的观点。此外，我们使用细胞膜电位探针来预测阳离子肽的体外活性。总之，这些发现提供了肽-细胞膜相互作用的机制见解，并可能为合理设计针对黑色素瘤的新型抗癌肽提供基础。

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引用次数: 0

Proline 110 is necessary for maintaining a compact helical arrangement in caveolin-1 脯氨酸110是维持小洞蛋白-1紧密螺旋排列所必需的。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-11 DOI: 10.1016/j.bpc.2025.107535

Katrina Brandmier, Kerney Jebrell Glover

Caveolin-1 (Cav1) is an integral membrane protein essential for the formation of caveolae, plasma microdomains implicated in signal transduction and mechanoprotection. Cav1 is comprised of three major alpha helices, but the topology these helices adopt remains unclear. Proline 110 is located between helix 1 and helix 2, and is hypothesized to enable Cav1 to adopt an intramembrane turn crucial for the cytosolic topology of Cav1. To assess the structural role of Proline 110, we utilized Förster resonance energy transfer (FRET) between native tryptophan (W128) and site-specifically labeled dansyl fluorophores to monitor conformational changes induced by the mutation of Proline 110 to Alanine (P110A). Static light scattering confirmed that all FRET constructs behaved monomerically, ensuring intramolecular energy transfer measurements. Our results show a significant decrease in FRET efficiency upon the P110A mutation consistent with a large conformational change. These findings support the critical role of P110 in maintaining the native topology of Cav1 and highlights the structural sensitivity of the intramembrane turn.

小窝蛋白-1 （Cav1）是一种完整的膜蛋白，对小窝的形成至关重要，涉及信号转导和机械保护的等离子体微域。Cav1由三个主要的α螺旋组成，但这些螺旋采用的拓扑结构尚不清楚。脯氨酸110位于螺旋1和螺旋2之间，据推测，它使Cav1能够采用膜内转向，这对Cav1的细胞质拓扑结构至关重要。为了评估脯氨酸110的结构作用，我们利用Förster共振能量转移（FRET）在天然色氨酸（W128）和位点特异性标记的丹酰荧光团之间监测脯氨酸110向丙氨酸（P110A）突变引起的构象变化。静态光散射证实，所有FRET结构表现为单体，确保分子内的能量转移测量。我们的研究结果显示，P110A突变后FRET效率显著下降，这与大的构象变化相一致。这些发现支持了P110在维持Cav1的天然拓扑结构中的关键作用，并强调了膜内转向的结构敏感性。

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引用次数: 0

SDS protein interactions SDS蛋白相互作用。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-10 DOI: 10.1016/j.bpc.2025.107534

Tsutomu Arakawa , Daisuke Ejima , Tomoto Ura , Teruo Akuta , Masamichi Oh-Ishi

Sodium dodecyl sulfate (SDS) is one of the most widely used detergents. Here, we discuss current knowledge regarding applications of SDS and its modes of interaction with proteins, particularly at low concentrations. SDS at 1–2 %, which is well above the critical micelle concentration, is commonly used to extract fully denatured and dissociated proteins and SDS polyacrylamide gel electrophoresis (SDS-PAGE) in various applications, especially proteomics. In contrast, low concentration SDS may have been relatively underutilized. Here, we demonstrate the use of 0.1 % SDS for decellularization and protein fractionation. Why is 0.1 % SDS unique? The interaction between SDS and proteins is complex and depends on both the conditions and the proteins involved. At 0.1 %, the effects of SDS appear to be intermediate between negligible and extensive binding, highlighting its potential for novel applications. Two milder anionic detergents, Sarkosyl and sodium N-lauroyglutamate, whose effects are similar in certain applications to those of low concentration SDS, were briefly discussed.

十二烷基硫酸钠（SDS）是应用最广泛的洗涤剂之一。在这里，我们讨论了目前关于SDS的应用及其与蛋白质相互作用模式的知识，特别是在低浓度下。SDS在1- 2%，远高于临界胶束浓度，通常用于提取完全变性和解离的蛋白质和SDS聚丙烯酰胺凝胶电泳（SDS- page）在各种应用中，特别是蛋白质组学。相比之下，低浓度SDS可能相对没有得到充分利用。在这里，我们演示了0.1% SDS用于脱细胞和蛋白质分离。为什么0.1% SDS是唯一的？SDS和蛋白质之间的相互作用是复杂的，取决于条件和所涉及的蛋白质。在0.1%时，SDS的作用介于可忽略不计和广泛结合之间，突出了其新应用的潜力。简要讨论了两种较温和的阴离子洗涤剂，萨科齐和n -月桂谷氨酸钠，它们在某些应用中的效果与低浓度SDS相似。

引用次数: 0

Molecular docking and density functional theory studies of flavonoids of Holy basil plant against COX-2 enzyme 罗勒类黄酮抗COX-2酶分子对接及密度泛函理论研究

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-10-06 DOI: 10.1016/j.bpc.2025.107533

Hari K.C. , Kumar Neupane , Khadka B. Chhetri , Rojina Ojha , Raj K. Acharya

Holy basil (Ocimum tenuiflorum) is primarily found in Nepal and India. In Ayurveda, it is commonly used as a traditional medicine to reduce pain, swelling, and various diseases. It has gained significant attention for its potential anti-inflammatory properties. One of the key targets associated with inflammation is Cyclooxygenase-2 (COX-2), an enzyme responsible for prostaglandin synthesis during the inflammatory response. In this study, we selected twenty flavonoids in the Holy Basil plant. These compounds were screened through Lipinski’s Rule of Five, followed by ADMET prediction. Virtual screening was conducted on the selected compounds against the COX-2 enzyme as a receptor using molecular docking techniques. Molecular docking study provides valuable insights at the molecular level into the interactions between Holy Basil compounds and COX-2. Furthermore, density functional computations were carried out utilizing the B3LYP method with the 6-311G basis, which is set to gain insight into the structural and electronic properties of the compounds. This study showcases the potential of flavonoids such as rhamnetin, Luteolin and kaempferol to act as anti-inflammatory agents, sparking further interest and research in this area.

圣罗勒（Ocimum tenuflorum）主要产于尼泊尔和印度。在阿育吠陀，它通常被用作一种传统药物来减轻疼痛、肿胀和各种疾病。它因其潜在的抗炎特性而受到广泛关注。与炎症相关的关键靶点之一是环氧化酶-2 (COX-2)，一种在炎症反应中负责前列腺素合成的酶。本研究从罗勒植物中提取了20种黄酮类化合物。这些化合物通过Lipinski 's Rule of Five进行筛选，然后进行ADMET预测。利用分子对接技术对选定的COX-2酶受体进行虚拟筛选。分子对接研究在分子水平上对罗勒化合物与COX-2的相互作用提供了有价值的见解。此外，利用6-311G基的B3LYP方法进行密度泛函计算，以深入了解化合物的结构和电子性质。这项研究展示了鼠李素、木犀草素和山奈酚等类黄酮作为抗炎剂的潜力，激发了这一领域的进一步兴趣和研究。

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引用次数: 0

Conformational transition of a polycationic hinge domain contributes to DNA binding 多阳离子铰链结构域的构象转变有助于DNA结合

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-09-26 DOI: 10.1016/j.bpc.2025.107531

Michael T. Harnish, Bill Pham, Avery B. Arons, Yingjie Xu, Elias J. Fernandez, Tongye Shen

Nuclear receptors (NRs) are multidomain, ligand-activated transcription factors that play critical physiological roles. While the structured DNA-binding domain (DBD) and ligand-binding domain (LBD) have been well characterized, the function of intrinsically disordered regions—such as the hinge between the LBD and DBD—remains unclear. To illuminate the role of the hinge, we conducted five-microsecond molecular dynamics simulations of thyroid hormone receptor (TRα) alone versus bound to DNA. We reveal that DNA binding induces a significant structural change in the hinge region (helical to unwound coil), with a potentially important role in the regulation of TRα activity. Previously, hinge helicity has been reported to drive oligomerization and the consequent inhibition of coactivator binding, and such DNA-induced transition may promote TR activation. Protein-DNA binding is found to be multivalent and contains the direct interaction of the hinge with the DNA minor groove in addition to the canonical recognition helix of the DBD with the major groove. Furthermore, the poly-Arg segment of the hinge has a direct and significant influence on DNA conformation. This interaction promotes a bent DNA phosphate backbone, which might further contribute to the protein-DNA recognition. On a global scale, DNA binding induces a “closed-to-open” conformational change thus reducing direct DBD-LBD interactions, which corroborates previous calorimetric binding studies. Overall, our results provide insight into the mechanism of DNA recognition and the resulting conformational dynamics of the TRα-DNA complex.

核受体是一种多结构域、配体激活的转录因子，在生理上起着至关重要的作用。虽然结构dna结合域（DBD）和配体结合域（LBD）已经被很好地表征，但内在无序区域的功能（如LBD和DBD之间的铰链）仍不清楚。为了阐明铰链的作用，我们进行了甲状腺激素受体（TRα）单独与结合DNA的5微秒分子动力学模拟。我们发现DNA结合诱导了铰链区域（螺旋到未缠绕线圈）的显著结构变化，在TRα活性的调节中具有潜在的重要作用。先前有报道称，铰链螺旋度可以驱动寡聚化，从而抑制共激活因子的结合，这种dna诱导的转变可能会促进TR的激活。发现蛋白质-DNA结合是多价的，除了DBD与主槽的典型识别螺旋外，还包括铰链与DNA小槽的直接相互作用。此外，铰链的poly-Arg片段对DNA构象有直接而显著的影响。这种相互作用促进弯曲的DNA磷酸主链，这可能进一步有助于蛋白质-DNA识别。在全球范围内，DNA结合诱导了“从封闭到开放”的构象变化，从而减少了DBD-LBD的直接相互作用，这证实了之前的量热结合研究。总的来说，我们的研究结果为DNA识别的机制和TRα-DNA复合物的构象动力学提供了见解。

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引用次数: 0

Antimicrobial peptide mechanism of action on S. aureus membranes determined by in vivo solid-state NMR 体内固体核磁共振测定抗菌肽对金黄色葡萄球菌膜的作用机制

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-09-24 DOI: 10.1016/j.bpc.2025.107532

Laila Zaatouf, Thierry Drujon, Astrid Walrant, Emmanuelle Sachon, Dror E. Warschawski

Staphylococcus aureus (S. aureus) is a Gram-positive pathogenic bacterium and a major cause of nosocomial infections. Between 20 % and 50 % of S. aureus strains are resistant to a wide range of antibiotics. DMS-DA6-NH₂ (DA6) is a novel antimicrobial peptide (AMP) that exhibits high efficacy against various bacterial strains, particularly S. aureus, by disrupting its membrane through an as-yet-unknown mechanism. We employed in vivo ²H solid state Nuclear Magnetic Resonance (NMR) to investigate the mode of action of AMPs on deuterated bacteria. This technique provides insights into membrane order and its changes with increasing AMP concentration. Our results enabled us to compare the mechanism of DA6 with those of AMPs with established modes of action. We found that DA6 induces pore formation in the membrane of S. aureus. This protocol serves as a template for determining the mechanisms of action of other peptides, an essential step for developing and patenting such drugs for the treatment of human diseases.

金黄色葡萄球菌（金黄色葡萄球菌）是一种革兰氏阳性致病菌，也是医院感染的主要原因。20%至50%的金黄色葡萄球菌菌株对多种抗生素具有耐药性。DMS-DA6-NH2 （DA6）是一种新型抗菌肽（AMP），通过一种未知的机制破坏其膜，对各种细菌菌株，特别是金黄色葡萄球菌表现出高效率。我们利用2H固态核磁共振（NMR）研究了AMPs对氘化细菌的作用模式。这项技术提供了对膜序及其随AMP浓度增加而变化的见解。我们的结果使我们能够将DA6的机制与具有既定作用模式的amp的机制进行比较。我们发现DA6可以诱导金黄色葡萄球菌的膜形成孔。该协议可作为确定其他多肽作用机制的模板，这是开发用于治疗人类疾病的此类药物并为其申请专利的重要步骤。

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引用次数: 0

K2P channels and ultrasound neuromodulation: A mechanosensitive memory perspective K2P通道和超声神经调节：机械敏感记忆的视角

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-09-22 DOI: 10.1016/j.bpc.2025.107530

Yuval Ben-Abu

Recent work by Ben Abu and Wolfson introduces the concept of ‘energetic memory’ in ion channels, providing a mechanistic framework for ultrasound neuromodulation. This discussion examines how K2P (two-pore domain potassium) channels serve as primary mediators of mechanosensitive memory due to their small size (0.5 μm radius), constitutive activity, and critical physiological roles. In contrast, larger Kv channels (5 μm) show intermediate sensitivity while Na⁺ channels (50 μm) remain largely unaffected, creating size-dependent responses. Nanoindentor experiments demonstrate sustained membrane hyperpolarization following mechanical compression, validating the theoretical predictions. The energetic memory model explains ultrasound therapy's clinical efficacy through preferential K2P channel compression, energy system adaptation, and prolonged recovery phases. This framework enables rational optimization of therapeutic protocols and extends to other mechanically-based interventions, fundamentally expanding our understanding of neural plasticity beyond traditional electrical mechanisms.

Ben Abu和Wolfson最近的工作介绍了离子通道中“能量记忆”的概念，为超声神经调节提供了一个机制框架。本文探讨了K2P（双孔结构域钾）通道如何由于其小尺寸（0.5 μm半径）、本构活性和关键的生理作用而成为机械敏感记忆的主要介质。相比之下，较大的Kv通道（5 μm）表现出中等灵敏度，而Na+通道（50 μm）基本不受影响，产生尺寸相关的响应。纳米压痕实验证明了机械压缩后膜的持续超极化，验证了理论预测。能量记忆模型通过优先压缩K2P通道、能量系统适应和延长恢复期来解释超声治疗的临床疗效。该框架能够合理优化治疗方案，并扩展到其他基于机械的干预措施，从根本上扩展了我们对传统电机制之外的神经可塑性的理解。

引用次数: 0