Biochimica et biophysica acta. Biomembranes最新文献_第2页

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 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub 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

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.

AMPs are usually modified or designed de novo, 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.

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.

抗菌肽（AMPs）是目前针对多重耐药病原体开发新抗生素的一种策略。amp的潜在抗生素活性与其两亲性和正电荷残基的存在有关，正电荷残基可能与带负电荷的细菌膜相互作用。相反，它们与真核生物中性带电膜的相互作用较低。这是amp可以区分真核和原核膜的主要原因。amp通常是经过修饰或重新设计的，并且可以通过在其序列中插入特定的氨基酸残基来改变其性质。为了帮助抗菌肽的合理设计，探讨其在靶细胞膜上可能引起的生物物理变化是有帮助的。因此，细菌和真核生物模型脂膜已被广泛用于这一目的。选择性结合、脂膜相互作用、膜包装、渗透性、水合作用和重组等参数有助于探索感兴趣的肽区域。这些参数可以用各种物理化学技术来研究，包括差示扫描量热法、x射线衍射、核磁共振和荧光光谱。这篇综述的目的是为主要的生物物理技术提供实用指南，用于利用模型膜探索amp的潜在抗生素活性，并检查脂肽相互作用，以确定这些抗菌肽的作用机制。这些技术确定肽是否与细菌膜特异性相互作用，给定AMP的首选细菌靶点，AMP的结合亲和力，潜在的孔形成及其几何形状，以及这些相互作用对细菌和真核生物膜的影响。

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引用次数: 0

Nanoscopic remodeling of lipid bilayers by cell-penetrating peptide penetratin 细胞穿透肽穿透素对脂质双层的纳米重塑。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-12-29 DOI: 10.1016/j.bbamem.2025.184496

Yasith Indigahawela Gamage, Jianjun Pan

Cell-penetrating peptides (CPPs) such as penetratin are known to traverse lipid membranes, yet the nanoscale structural consequences of their membrane interactions remain incompletely understood. Using atomic force microscopy (AFM), we visualized penetratin-induced remodeling in supported lipid bilayers (SLBs), focusing on discrete POPC bilayer patches whose exposed edges sensitively report early structural changes. In POPC patches, penetratin first accumulated at patch boundaries, forming elevated peripheral rings, and at higher concentrations generated shallow nanoscale pits across the patch interior. Continuous POPC bilayers exhibited a closely parallel pathway—elevated protrusions at 1 μM penetratin and widespread nanoscale pore-like depressions at 2–4 μM—indicating that similar peptide–lipid structures form even without membrane edges. Bilayers containing anionic POPS showed greatly enhanced susceptibility, progressing from peripheral depressions and aggregates to full fragmentation into nanoscale lipid–peptide particles, whereas cholesterol-containing bilayers remained largely resistant, developing only a few isolated deep defects. Our findings reveal an array of penetratin-induced remodeling events shaped by membrane composition and geometry, providing new mechanistic insight into how penetratin modulates membrane structure at the nanoscale.

众所周知，细胞穿透肽（CPPs）如穿透素可以穿过脂质膜，但其膜相互作用的纳米级结构后果仍不完全清楚。利用原子力显微镜（AFM），我们可视化了穿透素诱导的支持脂质双分子层（slb）重构，重点关注离散的POPC双分子层斑块，其暴露的边缘敏感地报告了早期结构变化。在POPC斑块中，穿透素首先在斑块边界积聚，形成升高的外围环，当浓度较高时，在斑块内部产生浅的纳米级凹坑。连续的POPC双分子层表现出紧密平行的通路- 1 μM处的凸起和2-4 μM处广泛的纳米级孔状凹陷，这表明即使没有膜边缘，也可以形成相似的肽脂结构。含有阴离子持久性有机污染物的双分子层表现出极大增强的易感性，从外周凹陷和聚集发展到完全破碎成纳米级脂质肽颗粒，而含有胆固醇的双分子层仍然具有很大的抗性，仅形成少数孤立的深度缺陷。我们的研究结果揭示了一系列由膜组成和几何形状决定的穿透素诱导的重塑事件，为穿透素如何在纳米尺度上调节膜结构提供了新的机制见解。

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引用次数: 0

Mechanistic insight into the role of lipoglycopeptide drugs in hepatotoxicity 脂糖肽类药物在肝毒性中的作用机制。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-12-29 DOI: 10.1016/j.bbamem.2025.184497

Akash Kumar Jha , Vetriselvan Subramaniyan , Raj Gupta , Arabinda Saha , Ashutosh Kumar

Understanding how antibiotics interact with membranes is crucial for predicting their off-target effects, particularly hepatotoxicity. This work compares two clinically important glycopeptide antibiotics, Teicoplanin and Oritavancin, using an integrative approach that combines in vivo pathology, lipid biophysics, drug-lipid interactions by NMR spectroscopy, and molecular dynamics simulations. Despite causing little direct disruption to lipid membranes, Teicoplanin produced significant hepatotoxicity, including increased liver enzymes and histopathological loss. Teicoplanin localises at the membrane–aqueous interface, where it forms stable surface-level interactions that have the potential to periodically disrupt membrane-associated processes. On the other hand, due to its deep insertion into the bilayer core, Oritavancin exhibited a more benign hepatic profile, despite causing stronger membrane perturbation. Long-term cellular stress is probably mitigated by this embedded configuration, which facilitates less interaction with membrane receptors. These findings demonstrate that glycopeptide-induced hepatotoxicity is governed by the topology and duration of membrane interactions rather than simply by their magnitude. The study promotes a lipid-centric framework for the logical development of safer, membrane-active treatments and emphasises the value of lipid membrane models and atomistic simulations as predictive tools in early-stage drug evaluation.

了解抗生素如何与细胞膜相互作用对于预测其脱靶效应，特别是肝毒性至关重要。这项工作比较了两种临床上重要的糖肽抗生素，Teicoplanin和Oritavancin，使用综合方法，结合体内病理，脂质生物物理学，核磁共振波谱的药物-脂质相互作用和分子动力学模拟。尽管Teicoplanin对脂质膜的直接破坏很小，但却产生了显著的肝毒性，包括肝酶增加和组织病理学损失。Teicoplanin定位于膜-水界面，在那里它形成稳定的表面相互作用，具有周期性破坏膜相关过程的潜力。另一方面，由于Oritavancin深入双层核心，尽管会引起更强的膜扰动，但却表现出更良性的肝脏特征。这种嵌入的结构可能减轻了长期的细胞应激，这有助于减少与膜受体的相互作用。这些发现表明，糖肽诱导的肝毒性是由膜相互作用的拓扑结构和持续时间决定的，而不仅仅是由它们的大小决定的。该研究促进了一个以脂质为中心的框架，用于更安全、膜活性治疗的逻辑开发，并强调了脂质膜模型和原子模拟作为早期药物评估预测工具的价值。

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引用次数: 0

Structural and dynamics of apoA-1 mimetic peptide lipid nanodisc assemblies: A molecular dynamics study 模拟apoA-1肽脂质纳米盘组装的结构和动力学：分子动力学研究。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-29 DOI: 10.1016/j.bbamem.2025.184495

Rohith Ravi , Evgeniy S. Salnikov , Burkhard Bechinger , Mounir Tarek

Apolipoprotein A-I (apoA-I) mimetic peptides, inspired by the principal protein component of high-density lipoprotein, self-assemble with lipids to form discoidal nanodiscs widely used in biomedical research and as versatile scaffolds for characterization of membrane proteins in structural biology. Here, we investigate the 14A apoA-I mimetic, quantifying its orientation around the lipid bilayer and identifying the interactions that are crucial for nanodisc stability and dynamics using all-atom molecular dynamics simulations. To assess model fidelity, we back-calculated solid-state NMR observables, namely ¹⁵N chemical shifts and ²H quadrupolar splittings from the trajectories and compared them with previously reported solid-state NMR data. The simulations support a dimeric, antiparallel, belt-like arrangement of 14A peptides around the discoidal bilayer, stabilized by

π - π

stacking between aromatic residues and by electrostatic and hydrophobic peptide–lipid interactions. These interactions yield structurally stable nanodiscs with pronounced heterogeneity in lipid ordering and bilayer thickness between the nanodisc center and rim. Collectively, our MD results provide atomistic evidence for previously hypothesized peptide–peptide and peptide–lipid interactions and clarify how amphipathic helices organize to form the rim of discoidal nanodiscs. These insights inform the rational design of apoA-I mimetics for biomedical applications and the optimization of nanodiscs as platforms for studying membrane proteins.

载脂蛋白A-I （apoA-I）模拟肽受到高密度脂蛋白主要蛋白质成分的启发，与脂质自组装形成盘状纳米盘，广泛应用于生物医学研究，并作为结构生物学中膜蛋白表征的多功能支架。在这里，我们研究了14A apoA-I模拟物，量化了它在脂质双分子层周围的取向，并利用全原子分子动力学模拟确定了对纳米盘稳定性和动力学至关重要的相互作用。为了评估模型的保真度，我们回溯计算了固态核磁共振观测值，即轨迹上的15N化学位移和2H四极分裂，并将其与先前报道的固态核磁共振数据进行了比较。模拟结果支持在圆盘状双分子层周围形成二聚体、反平行、带状排列的14A肽，通过芳香残基之间的π-π堆叠以及静电和疏水肽脂相互作用来稳定。这些相互作用产生了结构稳定的纳米圆盘，在纳米圆盘中心和边缘之间的脂质有序和双层厚度上具有明显的异质性。总的来说，我们的MD结果为先前假设的肽-肽和肽-脂相互作用提供了原子证据，并阐明了两亲螺旋如何组织形成盘状纳米圆盘的边缘。这些见解为合理设计用于生物医学应用的apoA-I模拟物和优化纳米盘作为研究膜蛋白的平台提供了信息。

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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 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub 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

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 in vitro 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.

RTX毒素是革兰氏阴性菌分泌的成孔毒素。它们以破坏宿主细胞膜的能力而闻名，其中包括各种人类细胞。这些毒素中特定赖氨酸残基的酰化对其溶血活性至关重要，但这种增强的确切机制尚不清楚。通过比较酰化和非酰化形式的MbxA的裂解活性，我们探讨了酰化在这种RTX毒素的成孔行为中的作用。我们的研究结果表明，在体外和活细胞中，MbxA与胆固醇的酰化特异性相互作用促进了膜的破坏。更具体地说，酰基化不是初始膜结合所必需的，但可以显著增强孔的形成。总的来说，我们的研究结果提供了调控MbxA毒素活性的分子决定因素的详细见解。我们强调了脂质组成（固醇）、酰化和膜破坏之间的复杂相互作用，从而促进了我们对RTX毒素发病机制的一般理解。

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引用次数: 0

TRAP mediated conformational changes of the human Sec61 channel TRAP介导的人类Sec61通道构象变化

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-24 DOI: 10.1016/j.bbamem.2025.184488

Nidhi Sorout, Volkhard Helms

The integral membrane pore Sec61 catalyzes the translocation of many secretory precursor proteins into the endoplasmic reticulum, as well as the insertion of transmembrane proteins into the cell and organellar membranes. Precursor proteins that possess weak signal peptides frequently require presence of the accessory membrane protein TRAP. Structural biology has recently established that TRAP shares several contact sites with Sec61, though not by an extended binding interface. However, how TRAP mechanistically supports the translocation of precursor proteins is still partially unresolved. Here, atomistic molecular dynamics simulations revealed that TRAP binding keeps Sec61 in a partially opened state, with looser packing of its transmembrane helices. TRAP maintained a partially opened Sec61 lateral gate and pore ring, shifting the plug helix towards an open conformation. These observations corroborate the existing model of how TRAP may support translocation of client precursor proteins with weak signal peptides.

整体膜孔Sec61催化许多分泌前体蛋白易位进入内质网，以及跨膜蛋白插入细胞和细胞器膜。具有弱信号肽的前体蛋白通常需要辅助膜蛋白TRAP的存在。结构生物学最近证实，TRAP与Sec61共享几个接触位点，尽管不是通过扩展的结合界面。然而，TRAP如何在机制上支持前体蛋白的易位仍然部分未解。在这里，原子分子动力学模拟显示，TRAP结合使Sec61处于部分开放状态，其跨膜螺旋的包装更松散。TRAP保持了部分打开的Sec61侧闸门和孔环，将桥塞螺旋转向开放构象。这些观察结果证实了TRAP如何支持客户前体蛋白与弱信号肽的易位的现有模型。

引用次数: 0

Effect of amyloid-beta 1–40 and 1–42 peptides on the lateral diffusion and signaling of receptor for advanced glycation endproducts (RAGE) 淀粉样蛋白- β 1-40和1-42肽对晚期糖基化终末产物（RAGE）受体横向扩散和信号传导的影响。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-19 DOI: 10.1016/j.bbamem.2025.184485

Chamari S. Wijesooriya , Sharifur Rahman , Emily A. Smith

The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that interacts with different ligands, including the amyloid-beta (Aβ) peptides, to initiate signaling pathways and create pro-inflammatory mediators. Receptor diffusion plays an important role in its functionality; for example, lateral mobility is needed for the assembly of signaling complexes. However, the effect of Aβ ligand binding on the diffusion of RAGE and its correlation with RAGE-mediated signaling have not been studied. This study investigated the impact of Aβ 1–40 and Aβ 1–42 on RAGE's lateral diffusion and MAPK signaling. Differing in length by only two amino acids, these two most prominent Aβ isoforms have differing cellular toxicities: Aβ 1–42 is considered the more toxic form. Single-particle tracking measurements showed that both Aβ 1–40 and Aβ 1–42 altered RAGE diffusion in HEK293 cells compared to a ligand untreated control, although the effects were different for each peptide. Aβ 1–42 treatment enhanced the activation of both p38 and p44/42 MAPKs via RAGE, whereas Aβ 1–40 treatment did not significantly increase p38 activation. These results are consistent with the greater toxicity of Aβ 1–42: p38 MAPK is often associated with stress-stimuli and inflammation whereas p44/42 MAPK is more commonly associated with growth factors and cell proliferation. The results show that differing cellular toxicities of Aβ 1–40 and Aβ 1–42 are also associated with divergent effects on RAGE diffusion and MAPK signal pathway activation.

晚期糖基化终产物受体（RAGE）是一种模式识别受体，它与不同的配体相互作用，包括淀粉样蛋白- β (a β)肽，启动信号通路并产生促炎介质。受体扩散在其功能中起重要作用；例如，信号复合物的组装需要横向移动。然而，Aβ配体结合对RAGE扩散的影响及其与RAGE介导的信号传导的相关性尚未得到研究。本研究探讨了Aβ 1-40和Aβ 1-42对RAGE的横向扩散和MAPK信号传导的影响。这两种最突出的Aβ同工异构体的长度仅相差两个氨基酸，它们具有不同的细胞毒性：Aβ 1-42被认为是毒性更大的形式。单颗粒跟踪测量显示，与未处理的配体对照相比，a β 1-40和a β 1-42都改变了RAGE在HEK293细胞中的扩散：a β 1-40处理导致RAGE扩散减慢，并增加RAGE进入受限膜域的次数。Aβ 1-42处理也通过RAGE增强了p38和p44/42 MAPKs的激活，而Aβ 1-40处理没有显著增加p38的激活。这些结果与Aβ 1-42更大的毒性一致：p38 MAPK通常与应激刺激和炎症有关，而p44/42 MAPK更常与生长因子和细胞增殖有关。结果表明，Aβ 1-40和Aβ 1-42的不同细胞毒性也与RAGE扩散和MAPK信号通路激活的不同作用有关。

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引用次数: 0

Bacterial cell susceptibility to the antimicrobial peptide MP1 depends on membrane lipid packing 细菌细胞对抗菌肽MP1的敏感性取决于膜脂包装。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-19 DOI: 10.1016/j.bbamem.2025.184486

L. Stefania Vargas-Velez, Florencia Hellriegel , Mariela R. Monti, Natalia Wilke

Polybia-MP1 is an antimicrobial peptide with broad-spectrum activity, but with varying efficacy against different bacterial strains. It is proposed to act on the cell membrane, and therefore, the higher tolerance of some strains may be attributed to differences in their membrane properties. Considering this hypothesis, we studied the biophysical properties of the membrane for bacteria with different susceptibility to the peptide. We found that high tolerance to the peptide correlates with lipid membranes of high microviscosity and stiffness, factors that in turn depend on lipid packing. We propose that high lipid packing slows peptide penetration into membranes and the subsequent disruption of the bilayer, limiting its action. Therefore, we conclude that lipid packing is an important factor determining the differences in susceptibility among bacteria. This interplay between peptide action and membrane properties hinders the development of bacterial resistance to the peptide, since alterations in lipid composition lead to various changes in membrane properties, which in turn have differential effects on cell function.

Polybia-MP1是一种广谱抗菌肽，但对不同菌株的抑菌效果不同。它被认为是作用于细胞膜上，因此，一些菌株的高耐受性可能归因于它们的膜特性的差异。考虑到这一假设，我们研究了不同细菌对肽的敏感性膜的生物物理特性。我们发现，对肽的高耐受性与高微粘度和硬度的脂质膜有关，而这些因素反过来又取决于脂质包装。我们提出，高脂质包装减缓肽渗透到膜和随后的双分子层的破坏，限制其作用。因此，我们得出结论，脂质堆积是决定细菌敏感性差异的重要因素。肽作用和膜特性之间的相互作用阻碍了细菌对肽的耐药性的发展，因为脂质组成的改变导致膜特性的各种变化，而这些变化反过来对细胞功能有不同的影响。

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引用次数: 0

Tubulation of membrane sheets by curvature-inducing proteins 曲率诱导蛋白对膜片的管化作用。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-18 DOI: 10.1016/j.bbamem.2025.184484

Emad Ghazizadeh , Mahdi Zeidi , Wylie Stroberg

The endoplasmic reticulum (ER) is a highly dynamic organelle that undergoes continuous remodeling between tubular and sheet-like structures, driven by curvature-inducing proteins and membrane mechanics. Understanding the physical principles underlying ER shape transitions is crucial for elucidating its role in cellular homeostasis and disease. In this study, we use a mesoscopic model of membrane-protein interactions to investigate how intrinsic curvature, protein concentration, and membrane stiffening collectively regulate ER tubulation. Our results demonstrate that the critical concentration for tubulation depends nonlinearly on intrinsic curvature due to a competition between adsorption and remodeling ability. Additionally, increased membrane stiffness upon protein adsorption enhances tubulation efficiency at lower intrinsic curvatures and changes tubule geometry at higher intrinsic curvatures. Phase diagrams are constructed to map the conditions necessary for membrane remodeling, revealing critical protein concentration thresholds for ER transformation. These findings provide a quantitative framework for ER shape regulation, offering insights into how different curvature-inducing proteins coordinate ER morphogenesis.

内质网（ER）是一个高度动态的细胞器，在曲率诱导蛋白和膜力学的驱动下，在管状结构和片状结构之间经历不断的重塑。了解内质网形状转变的物理原理对于阐明其在细胞稳态和疾病中的作用至关重要。在这项研究中，我们使用膜-蛋白质相互作用的介观模型来研究内在曲率、蛋白质浓度和膜硬化如何共同调节内质网微管。我们的研究结果表明，由于吸附和重塑能力之间的竞争，管状的临界浓度非线性地依赖于本征曲率。此外，蛋白质吸附时膜刚度的增加提高了低固有曲率下的管化效率，并改变了高固有曲率下的管的几何形状。构建相图来绘制膜重塑所需的条件，揭示ER转化的关键蛋白质浓度阈值。这些发现为内质网形状调节提供了一个定量框架，为了解不同的曲率诱导蛋白如何协调内质网形态发生提供了见解。

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引用次数: 0

Contribution to the special BBA issue dedicated to Joachim Seelig from lipid bilayers to the innate immune system 为Joachim Seelig从脂质双分子层到先天免疫系统的BBA特刊撰稿。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Biomembranes

Pub Date : 2025-11-11 DOI: 10.1016/j.bbamem.2025.184483

Anna Seelig

This personal review in memory of Joachim Seelig covers half a century of membrane biophysics. The topics chosen give insight into the structure and function of our innate immune system, consisting in the membranes covering the external and internal body surfaces in contact with the outside world. Their core is the lipid bilayer in its liquid crystalline state. We investigated its average structure and fluidity by deuterium-nuclear magnetic resonance spectroscopy (D-NMR) using selectively deuterated lipids. Close to the lipid-water interface, lipids retain a defined average structure with the glycerol backbone oriented perpendicular to the membrane surface. The characteristic structure of lipids remains in the presence of transmembrane proteins and guarantees a tight membrane packing near the aqueous phases. The order of lipid segments remains approximately constant decreasing only towards the membrane center. Were cells surrounded by lipids only, hydrophobic molecules would nevertheless penetrate the membranes and reach the nucleus, the smaller ones more rapidly and the larger one more slowly. To protect cells from intruding mutagenic compounds, a significant number of defense proteins have evolved, including ATP binding cassette (ABC) transporters and pattern recognition receptors (PRR). Interestingly, the different defense proteins recognize compounds that carry specific hydrogen bond acceptor patterns and could interfere with DNA or RNA. ABC transporters and pattern recognition receptors remove them from the lipid bilayer before they reach the cytosol to prevent mutagenesis. While these proteins are well known to contribute to multidrug resistance (MDR), their significant role in innate immunity only starts to emerge.

这篇纪念约阿希姆·西利格的个人回顾涵盖了半个世纪的膜生物物理学。所选择的主题可以深入了解我们先天免疫系统的结构和功能，包括覆盖与外界接触的身体内外表面的膜。它们的核心是处于液晶状态的脂质双分子层。采用选择性氘化脂质，用氘核磁共振谱（D-NMR）研究了其平均结构和流动性。靠近脂-水界面，脂质保持一个确定的平均结构，甘油主链垂直于膜表面。在跨膜蛋白存在的情况下，脂质的特征结构保持不变，并保证水相附近的膜紧密堆积。脂质片段的顺序大致保持不变，仅向膜中心方向递减。如果细胞仅被脂质包围，疏水分子仍会穿透细胞膜到达细胞核，较小的分子更快，较大的分子更慢。为了保护细胞免受诱变化合物的入侵，大量的防御蛋白已经进化出来，包括ATP结合盒（ABC）转运蛋白和模式识别受体（PRR）。有趣的是，不同的防御蛋白识别携带特定氢键受体模式的化合物，并可能干扰DNA或RNA。ABC转运蛋白和模式识别受体在它们到达细胞质之前将它们从脂质双分子层移除以防止突变。虽然众所周知，这些蛋白质有助于多药耐药（MDR），但它们在先天免疫中的重要作用才刚刚开始显现。

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引用次数: 0