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Effect of γ-Oryzanol on the LE-LC Phase Coexistence Region of DPPC Langmuir Monolayer. γ-谷维醇对DPPC Langmuir单层LE-LC相共存区的影响
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-06-03 DOI: 10.1007/s00232-023-00288-8
Raghavendra, Bharat Kumar, Siva N Chari

We have studied the effect of relative composition of γ-Oryzanol (γ-Or) on the liquid expanded-liquid condensed phase coexistence region in the mixed Langmuir monolayer of γ-Or and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules at air-water interface. The surface manometry studies at a fixed temperature show that the mixture of γ-Or and DPPC forms a stable monolayer at air-water interface. As the relative composition of γ-Or increases the range of area per molecule over which the coexistence of liquid expanded (LE)-liquid condensed (LC) phases exists reduces. Although the LE-LC phase coexistence corresponds to the first-order phase transition, the slope of the surface pressure-area per molecule isotherm is non-zero. Earlier studies have attributed the non-zero slope in LE-LC phase coexistence region to the influence of the strain between the ordered LC phase and disordered LE phase. The effect of strain on the coexistence of LE-LC phases can be studied in terms of molecular density-strain coupling. Our analysis of the liquid condensed-liquid expanded coexistence region in the isotherms of mixed monolayers of DPPC and γ-Or shows that with the increase in the mole fraction of sterol in the mixed monolayer the molecular lateral density-strain coupling increases. However, at 0.6 mole fraction of γ-Or in the mixed monolayer the coupling decreases. This is corroborated by the observation of minimum Gibb's free energy of the mixed monolayer at this relative composition of γ-Or indicating better packing of molecules.

本文研究了γ-谷米醇(γ-Or)的相对组成对γ-Or和1,2-双棕榈酰- n-甘油-3-磷酸胆碱(DPPC)分子在空气-水界面混合Langmuir单层中液胀-液凝聚共存区的影响。在固定温度下的表面测压研究表明,γ-Or和DPPC的混合物在空气-水界面形成稳定的单层。随着γ-Or相对组成的增加,液相膨胀相(LE)-液相凝聚相(LC)共存的分子面积范围减小。虽然l - lc相共存对应于一阶相变,但每分子等温线的表面压力-面积斜率不为零。早期的研究将LE-LC相共存区的非零斜率归因于有序LC相和无序LE相之间应变的影响。应变对LE-LC相共存的影响可以从分子密度-应变耦合的角度来研究。对DPPC和γ-Or混合单分子膜等温线上的液凝-液胀共存区分析表明,随着混合单分子膜中甾醇摩尔分数的增加,分子侧密度-应变耦合增大。然而,当混合单层中γ-Or的摩尔分数为0.6时,耦合减弱。在γ-Or的相对组成下,观察到混合单层的最小吉布自由能证实了这一点,表明分子的填充更好。
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引用次数: 0
Cationic Proteins Rich in Lysine Residue Trigger Formation of Non-bilayer Lipid Phases in Model and Biological Membranes: Biophysical Methods of Study. 富含赖氨酸残基的阳离子蛋白质触发模型和生物膜中非双层脂质相的形成:生物物理研究方法。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI: 10.1007/s00232-023-00292-y
Meiyi Li, Edward S Gasanoff

Cationic membrane-active toxins are the most abundant group of proteins in the venom of snakes and insects. Cationic proteins such as cobra venom cytotoxin and bee venom melittin are known for their pharmacological reactions including anticancer and antimicrobial effects which arise from the toxin-induced alteration in the dynamics and structure of plasma membranes and membranes of organelles. It has been established that these cationic toxins trigger the formation of non-bilayer lipid phase transitions in artificial and native mitochondrial membranes. Remarkably, the toxin-induced formation of non-bilayer lipid phase increases at certain conditions mitochondrial ATP synthase activity. This observation opens an intriguing avenue for using cationic toxins in the development of novel drugs for the treatment of cellular energy deficiency caused by aging and diseases. This observation also warrants a thorough investigation of the molecular mechanism(s) of lipid phase polymorphisms triggered by cationic proteins. This article presents a review on the application of powerful biophysical methods such as resonance spectroscopy (31P-, 1H-, 2H-nuclear magnetic resonance, and electron paramagnetic resonance), luminescence, and differential scanning microcalorimetry in studies of non-bilayer lipid phase transitions triggered by cationic proteins in artificial and biological membranes. A phenomenon of the triggered by cationic proteins the non-bilayer lipid phase transitions occurring within 10-2-10-11 s is discussed in the context of potential pharmacological applications of cationic proteins. Next to the ATP dimer is an inverted micelle made of cardiolipin that serves as a vehicle for the transport of H+ ions from the intra-crista space to the matrix. It is proposed that such inverted micelles are triggered by the high density of H+ ions and the cationic proteins rich in lysine residue which compete with the conserved lysine residues of the ATP synthase rotor for binding to cardiolipin in the inner mitochondrial membrane and perturb the bilayer lipid packing of cristae. Phospholipids with a blue polar head represent cardiolipin and those with a red polar head represent other phospholipids found in the crista membrane.

阳离子膜活性毒素是蛇和昆虫毒液中含量最丰富的一组蛋白质。已知阳离子蛋白如眼镜蛇毒素细胞毒素和蜂毒蜂毒肽的药理学反应,包括由毒素诱导的质膜和细胞器膜的动力学和结构改变引起的抗癌和抗微生物作用。已经证实,这些阳离子毒素触发人工和天然线粒体膜中非双层脂质相变的形成。值得注意的是,毒素诱导的非双层脂质相的形成在某些条件下增加了线粒体ATP合酶的活性。这一观察结果为利用阳离子毒素开发治疗衰老和疾病引起的细胞能量缺乏的新药开辟了一条有趣的途径。这一观察结果也保证了对阳离子蛋白引发的脂相多态性的分子机制进行彻底研究。本文综述了共振波谱(31P-、1H-、2H-核磁共振和电子顺磁共振)、发光和差示扫描微量热法等强大的生物物理方法在研究阳离子蛋白在人工和生物膜中引发的非双层脂质相变中的应用。在阳离子蛋白的潜在药理学应用的背景下,讨论了由阳离子蛋白触发的在10-2-10-11秒内发生的非双层脂质相变的现象。ATP二聚体旁边是一个由心磷脂制成的倒置胶束,它是H+离子从嵴内空间运输到基质的载体。有人提出,这种反向胶束是由高密度的H+离子和富含赖氨酸残基的阳离子蛋白触发的,这些阳离子蛋白与ATP合酶转子的保守赖氨酸残留竞争,与线粒体内膜中的心磷脂结合,并干扰嵴的双层脂质堆积。蓝色极性头的磷脂代表心磷脂,红色极性头代表嵴膜中的其他磷脂。
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引用次数: 0
Host Lipid Manipulation by Intracellular Bacteria: Moonlighting for Immune Evasion. 细胞内细菌对宿主脂质的操纵:免疫逃避的月光。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-11-08 DOI: 10.1007/s00232-023-00296-8
Naveen Challagundla, Deepti Phadnis, Aakriti Gupta, Reena Agrawal-Rajput

Lipids are complex organic molecules that fulfill energy demands and sometimes act as signaling molecules. They are mostly found in membranes, thus playing an important role in membrane trafficking and protecting the cell from external dangers. Based on the composition of the lipids, their fluidity and charge, their interaction with embedded proteins vary greatly. Bacteria can hijack host lipids to satisfy their energy needs or to conceal themselves from host cells. Intracellular bacteria continuously exploit host, from their entry into host cells utilizing host lipid machinery to exiting through the cells. This acquisition of lipids from host cells helps in their disguise mechanism. The current review explores various mechanisms employed by the intracellular bacteria to manipulate and acquire host lipids. It discusses their role in manipulating host membranes and the subsequence impact on the host cells. Modulating these lipids in macrophages not only serve the purpose of the pathogen but also modulates the macrophage energy metabolism and functional state. Additionally, we have explored the intricate pathogenic relationship and the potential prospects of using this knowledge in lipid-based therapeutics to disrupt pathogen dominance.

脂质是满足能量需求的复杂有机分子,有时充当信号分子。它们大多存在于膜中,因此在膜运输和保护细胞免受外部危险方面发挥着重要作用。根据脂质的组成、流动性和电荷,它们与嵌入蛋白质的相互作用差异很大。细菌可以劫持宿主脂质以满足其能量需求或向宿主细胞隐藏自己。细胞内细菌不断利用宿主,从利用宿主脂质机制进入宿主细胞到通过细胞离开。从宿主细胞中获取脂质有助于它们的伪装机制。目前的综述探讨了细胞内细菌操纵和获取宿主脂质的各种机制。它讨论了它们在操纵宿主膜中的作用以及随后对宿主细胞的影响。调节巨噬细胞中的这些脂质不仅可以达到病原体的目的,还可以调节巨噬细胞的能量代谢和功能状态。此外,我们还探索了复杂的致病关系,以及将这一知识用于基于脂质的治疗以破坏病原体优势的潜在前景。
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引用次数: 0
The Functionality of Membrane-Inserting Proteins and Peptides: Curvature Sensing, Generation, and Pore Formation. 膜插入蛋白和多肽的功能:曲率传感、生成和孔隙形成。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-08-31 DOI: 10.1007/s00232-023-00289-7
Chandra Has, Sovan Lal Das

Proteins and peptides with hydrophobic and amphiphilic segments are responsible for many biological functions. The sensing and generation of membrane curvature are the functions of several protein domains or motifs. While some specific membrane proteins play an essential role in controlling the curvature of distinct intracellular membranes, others participate in various cellular processes such as clathrin-mediated endocytosis, where several proteins sort themselves at the neck of the membrane bud. A few membrane-inserting proteins form nanopores that permeate selective ions and water to cross the membrane. In addition, many natural and synthetic small peptides and protein toxins disrupt the membrane by inducing nonspecific pores in the membrane. The pore formation causes cell death through the uncontrolled exchange between interior and exterior cellular contents. In this article, we discuss the insertion depth and orientation of protein/peptide helices, and their role as a sensor and inducer of membrane curvature as well as a pore former in the membrane. We anticipate that this extensive review will assist biophysicists to gain insight into curvature sensing, generation, and pore formation by membrane insertion.

具有疏水和两亲性片段的蛋白质和肽具有许多生物学功能。膜曲率的感知和产生是几个蛋白质结构域或基序的功能。虽然一些特定的膜蛋白在控制不同细胞膜的曲率方面起着重要作用,但其他的膜蛋白参与各种细胞过程,如网格蛋白介导的内吞作用,其中一些蛋白质在膜芽的颈部进行自我分类。一些插入膜的蛋白质形成纳米孔,通过选择性离子和水穿过膜。此外,许多天然和合成的小肽和蛋白毒素通过诱导膜上的非特异性孔来破坏膜。孔的形成通过内部和外部细胞内容物之间不受控制的交换导致细胞死亡。在本文中,我们讨论了蛋白质/肽螺旋的插入深度和方向,以及它们作为膜曲率的传感器和诱导剂以及膜孔形成物的作用。我们期望这一广泛的综述将有助于生物物理学家深入了解膜插入的曲率传感、产生和孔隙形成。
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引用次数: 0
Track and Field of the Journal of Membrane Biology. 《膜生物学杂志》田径项目。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 DOI: 10.1007/s00232-023-00298-6
Alexey S Ladokhin
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引用次数: 0
Exploration of the Catalytic Cycle Dynamics of Vigna Radiata H+-Translocating Pyrophosphatases Through Hydrogen-Deuterium Exchange Mass Spectrometry. 氢-氘交换质谱法研究辐射薇纳H+-易位焦磷酸酶的催化循环动力学。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-11-13 DOI: 10.1007/s00232-023-00295-9
Li-Kun Huang, Yi-Cyuan Huang, Pin-Chuan Chen, Ching-Hung Lee, Shih-Ming Lin, Yuan-Hao Howard Hsu, Rong-Long Pan

Vigna radiata H+-translocating pyrophosphatases (VrH+-PPases, EC 3.6.1.1) are present in various endomembranes of plants, bacteria, archaea, and certain protozoa. They transport H+ into the lumen by hydrolyzing pyrophosphate, which is a by-product of many essential anabolic reactions. Although the crystal structure of H+-PPases has been elucidated, the H+ translocation mechanism of H+-PPases in the solution state remains unclear. In this study, we used hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (MS) to investigate the dynamics of H+-PPases between the previously proposed R state (resting state, Apo form), I state (intermediate state, bound to a substrate analog), and T state (transient state, bound to inorganic phosphate). When hydrogen was replaced by proteins in deuterium oxide solution, the backbone hydrogen atoms, which were exchanged with deuterium, were identified through MS. Accordingly, we used deuterium uptake to examine the structural dynamics and conformational changes of H+-PPases in solution. In the highly conserved substrate binding and proton exit regions, HDX-MS revealed the existence of a compact conformation with deuterium exchange when H+-PPases were bound with a substrate analog and product. Thus, a novel working model was developed to elucidate the in situ catalytic mechanism of pyrophosphate hydrolysis and proton transport. In this model, a proton is released in the I state, and the TM5 inner wall serves as a proton piston.

辐射Vigna radiata H+-易位焦磷酸酶(VrH+-PPases, EC 3.6.1.1)存在于植物、细菌、古细菌和某些原生动物的各种膜中。它们通过水解焦磷酸盐将H+输送到管腔中,焦磷酸盐是许多基本合成代谢反应的副产物。虽然已经阐明了H+-PPases的晶体结构,但H+-PPases在溶液状态下的H+易位机制尚不清楚。在这项研究中,我们使用氢-氘交换(HDX)结合质谱(MS)来研究H+-PPases在先前提出的R态(静息态,载脂蛋白形式),I态(中间态,结合底物类似物)和T态(瞬态,结合无机磷酸盐)之间的动力学。在氧化氘溶液中,当氢被蛋白质取代时,通过质谱法确定了与氘交换的主氢原子。因此,我们利用氘摄取来研究溶液中H+-PPases的结构动力学和构象变化。在高度保守的底物结合区和质子出口区,HDX-MS显示,当H+-PPases与底物类似物和产物结合时,存在致密的氘交换构象。因此,建立了一个新的工作模型来阐明焦磷酸盐水解和质子转运的原位催化机理。在这个模型中,一个质子在I状态下被释放,TM5内壁起到质子活塞的作用。
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引用次数: 0
Correction: Hans Ussing Memorial Issue: Epithelial Membrane Transport. 更正:汉斯·乌辛纪念问题:上皮膜运输。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 DOI: 10.1007/s00232-023-00290-0
Stanley G Schultz, Alexander Leaf
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引用次数: 0
Research Progress on TRPA1 in Diseases. TRPA1在疾病中的研究进展
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-04-11 DOI: 10.1007/s00232-023-00277-x
Jiajing Li, Hongfei Zhang, Qian Du, Junyu Gu, Jiangbo Wu, Qi Liu, Zhuo Li, Ting Zhang, Jingyu Xu, Rui Xie

For a long time, the physiological activity of TRP ion channels and the response to various stimuli have been the focus of attention, and the physiological functions mediated by ion channels have subtle links with the occurrence of various diseases. Our group has been engaged in the study of ion channels. In recent years, the report rate of TRPA1, the only member of the TRPA subfamily in the newly described TRP channel, has been very high. TRPA1 channels are not only abundantly expressed in peptidergic nociceptors but are also found in many nonneuronal cell types and tissues, and through the regulation of Ca2+ influx, various neuropeptides and signaling pathways are involved in the regulation of nerves, respiration, circulation, and various diseases and inflammation throughout the body. In this review, we mainly summarize the effects of TRPA1 on various systems in the body, which not only allows us to have a more systematic and comprehensive understanding of TRPA1 but also facilitates more in-depth research on it in the future.

长期以来,TRP离子通道的生理活性和对各种刺激的反应一直是人们关注的焦点,离子通道介导的生理功能与各种疾病的发生有着微妙的联系。我们组一直从事离子通道的研究。近年来,新描述的TRP通道中唯一的TRPA亚家族成员TRPA1的报道率非常高。TRPA1通道不仅在多肽性伤害感受器中大量表达,而且在许多非神经元细胞类型和组织中也有发现,通过调节Ca2+内流,各种神经肽和信号通路参与全身神经、呼吸、循环和各种疾病和炎症的调节。在这篇综述中,我们主要总结了TRPA1对机体各系统的作用,这不仅可以让我们对TRPA1有一个更系统和全面的了解,也有助于我们在未来对其进行更深入的研究。
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引用次数: 0
Role of Hydrophobic Amino-Acid Side-Chains in the Narrow Selectivity Filter of the CFTR Chloride Channel Pore in Conductance and Selectivity. 疏水性氨基酸侧链在CFTR氯化物通道孔的窄选择性过滤器中的导电性和选择性作用。
IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-10-12 DOI: 10.1007/s00232-023-00294-w
Paul Linsdell

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Structural analysis of CFTR has identified a narrow, hydrophobic region close to the extracellular end of the open channel pore that may function as a selectivity filter. The present study combines comprehensive mutagenesis of hydrophobic amino-acid side-chains within the selectivity filter with functional evaluation of channel Cl- conductance and anion selectivity. Among these hydrophobic amino-acids, one (F337) appears to play a dominant role in determining both conductance and selectivity. Anion selectivity appears to depend on both side-chain size and hydrophobicity at this position. In contrast, conductance is disrupted by all F337 mutations, suggesting that unique interactions between permeating Cl- ions and the native phenylalanine side-chain are important for conductance. Surprisingly, a positively charged lysine side-chain can be substituted for several hydrophobic residues within the selectivity filter (including F337) with only minor changes in pore function, arguing against a crucial role for overall hydrophobicity. These results suggest that localized interactions between permeating anions and amino-acid side-chains within the selectivity filter may be more important in determining pore functional properties than are global features such as overall hydrophobicity.

囊性纤维化是由囊性纤维化跨膜电导调节因子(CFTR)阴离子通道的突变引起的。CFTR的结构分析已经确定了一个靠近开放通道孔细胞外端的狭窄疏水区域,该区域可能起到选择性过滤器的作用。本研究将选择性过滤器内疏水性氨基酸侧链的综合诱变与通道氯电导和阴离子选择性的功能评估相结合。在这些疏水性氨基酸中,一种(F337)似乎在决定电导和选择性方面发挥着主导作用。阴离子选择性似乎取决于该位置的侧链大小和疏水性。相反,电导被所有F337突变破坏,这表明渗透的Cl-离子和天然苯丙氨酸侧链之间的独特相互作用对电导很重要。令人惊讶的是,带正电的赖氨酸侧链可以取代选择性过滤器(包括F337)内的几个疏水残基,孔功能只有微小的变化,这与整体疏水性的关键作用相反。这些结果表明,在确定孔功能性质方面,选择性过滤器内渗透阴离子和氨基酸侧链之间的局部相互作用可能比整体特征(如整体疏水性)更重要。
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引用次数: 0
Forces and Flows at Cell Surfaces. 细胞表面的力和流。
IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-09-29 DOI: 10.1007/s00232-023-00293-x
Aurelia R Honerkamp-Smith
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引用次数: 0
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Journal of Membrane Biology
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