Biophysical chemistry最新文献_第2页

Modulation of islet amyloid polypeptide induced β-cell toxicity and amyloid formation by serum albumin proteins 胰岛淀粉样蛋白多肽诱导β细胞毒性和淀粉样蛋白形成的调节

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-12-13 DOI: 10.1016/j.bpc.2025.107565

Alexander Zhyvoloup , Zachary Ridgway , Ananya Prashanth , Daniel P. Raleigh

Human islet amyloid polypeptide (hIAPP, also known as amylin) is a 37-residue neuropancreatic hormone implicated in the progression of type 2 diabetes. hIAPP is soluble and partially structured under physiological conditions, but misfolds to form amyloid deposits in the islets of Langerhans in type 2 diabetes. Along the misfolding pathway, hIAPP forms species that are toxic to pancreatic β-cells, resulting in decreased β-cell function and mass. Serum albumin proteins are a key component of blood plasma and interstitial fluids and are omnipresent in mammalian cell culture media. Immortalized β-cell lines are widely used as model systems for mechanistic studies of hIAPP-induced cytotoxicity and for screening potential inhibitors of hIAPP toxicity. The effects of bovine serum albumin (BSA), human serum albumin (HSA) and fetal bovine serum (FBS) on hIAPP cytotoxicity are examined and the effects of BSA and HSA on hIAPP amyloid formation are explored. The time required for IAPP to form amyloid is lengthened by sub stoichiometric concentrations of BSA and HSA. Cell permeability and cell viability assays with cultured INS 832–13 pancreatic β-cells reveal that BSA, HSA, and FBS reduce hIAPP cytotoxicity. Partial protection against treatment with 40 μM hIAPP is observed for serum albumin concentrations that are only one tenth (=3.75 μM) of the normal amount present in a regular complete cell media containing 10 % FBS. The implications for in vitro assays of hIAPP toxicity and studies of hIAPP amyloid inhibitors are discussed.

人胰岛淀粉样蛋白多肽（hIAPP，也称为胰淀素）是一种37-残基的神经胰腺激素，与2型糖尿病的进展有关。hIAPP在生理条件下是可溶的和部分结构化的，但在2型糖尿病患者的朗格汉斯胰岛中错误折叠形成淀粉样蛋白沉积。沿着错误折叠途径，hIAPP形成对胰腺β细胞有毒的物质，导致β细胞功能和质量下降。血清白蛋白是血浆和间质液的关键成分，在哺乳动物细胞培养基中无处不在。永生化β细胞系被广泛用作hIAPP诱导细胞毒性机制研究和筛选hIAPP毒性潜在抑制剂的模型系统。研究了牛血清白蛋白（BSA）、人血清白蛋白（HSA）和胎牛血清（FBS）对hIAPP细胞毒性的影响，并探讨了BSA和HSA对hIAPP淀粉样蛋白形成的影响。BSA和HSA的亚化学计量浓度延长了IAPP形成淀粉样蛋白所需的时间。培养的INS 832-13胰腺β细胞的细胞通透性和细胞活力测定显示，BSA、HSA和FBS可降低hIAPP的细胞毒性。当血清白蛋白浓度仅为含有10%胎牛血清的正常完整细胞培养基的十分之一（=3.75 μM）时，观察到对40 μM hIAPP处理的部分保护作用。本文讨论了hIAPP体外毒性测定和hIAPP淀粉样蛋白抑制剂研究的意义。

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引用次数: 0

The effect of lipid saturation on the formation of styrene maleic acid lipid nanoparticles 脂质饱和度对苯乙烯马来酸脂质纳米颗粒形成的影响

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-12-13 DOI: 10.1016/j.bpc.2025.107566

Emma A. Gordon , Evelyn A. Okorafor , Indra D. Sahu , Kevin M. Burridge , Muhammad Zeeshan Shah , Onisha Thapa , Dominik Konkolewicz , Gary A. Lorigan

The ability to use styrene maleic acid (SMA) to solubilize membrane proteins has been of significant interest. The formation of the lipid nanodiscs and extraction of the proteins without the use of detergent allows for the study of these membrane proteins in a more native environment. Traditional mimetic systems, such as micelles, bicelles, and liposomes all have compatibility limitations in their ability to provide a native environment for the protein. Lipid composition plays a significant role in the compatibility of these mimetic systems with membrane proteins. In this study, lipids with varying degrees of saturation are used to assess the efficacy of the SMA polymer in forming styrene maleic acid lipid nanoparticles (SMALPs). Lipids ranging from fully saturated to fully unsaturated are used along with two SMA polymers with various hydrophobic tail lengths. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) are used to characterize the liposomes and SMALPs. Continuous Wave-Electron Paramagnetic Resonance Spectroscopy (CW-EPR) is used to understand the effect of SMA on a spin-labeled membrane protein incorporated in the SMALP system. Results show the dynamic properties of membrane proteins incorporated in SMALPs are dependent on SMA polymer tail length as well as the lipid saturation. Lineshape analysis shows evidence of the hydrophobic tail of the SMA playing a role in how the protein is positioned within the SMALPs.

利用苯乙烯马来酸（SMA）溶解膜蛋白的能力已经引起了人们极大的兴趣。在不使用洗涤剂的情况下，脂质纳米盘的形成和蛋白质的提取允许在更自然的环境中研究这些膜蛋白。传统的模拟系统，如胶束、单束和脂质体，在为蛋白质提供天然环境方面都有兼容性限制。脂质组成在这些模拟系统与膜蛋白的相容性中起着重要作用。在这项研究中，不同饱和度的脂质被用来评估SMA聚合物在形成苯乙烯马来酸脂质纳米颗粒（SMALPs）中的功效。脂质范围从完全饱和到完全不饱和，与两种具有不同疏水尾长度的SMA聚合物一起使用。采用动态光散射（DLS）和透射电子显微镜（TEM）对脂质体和SMALPs进行了表征。使用连续波电子顺磁共振波谱（CW-EPR）来了解SMA对纳入smmp系统的自旋标记膜蛋白的影响。结果表明，SMALPs中膜蛋白的动态特性取决于SMA聚合物的尾长和脂质饱和度。线形分析显示，SMA的疏水尾部在蛋白质如何定位在SMALPs中发挥作用。

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引用次数: 0

Protonation and protein folding: Insights from single-molecule fluorescence 质子化和蛋白质折叠：来自单分子荧光的见解

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-12-11 DOI: 10.1016/j.bpc.2025.107564

Vivek Pandey , Nikky Sharma , Tejasvi Pandey , Rajinder Singh Kaundal

Protein folding and protonation are deeply interconnected. Changes in the charge states of ionizable residues alter the local electrostatics and effective pKa values, influencing how proteins navigate their conformational landscapes. These protonation events can stabilize intermediates, guide folding pathways, and introduce kinetic diversity that support functional adaptability. Thus, understanding folding–protonation coupling has become a major focus of protein science. To probe these complex dynamics, increasingly sophisticated methodologies are required. Among them, single-molecule fluorescence (SMF) techniques have emerged as particularly powerful tools, providing unprecedented resolution of folding processes coupled to protonation. Approaches such as smFRET, fluorescence lifetime analysis, and rapid pH-jump experiments make it possible to observe events in exquisite detail. They reveal intermediates that escape detection in ensemble studies, capture heterogeneous subpopulations, and uncover rare, transient events that are critical to biological function. Building on these methodological advances, several case studies illustrate how protonation shapes biological outcomes for instance, histidine-rich domains function as molecular pH sensors, viral fusion proteins exploit protonation-triggered folding to mediate host entry, and engineered bio-switches harness pKa-dependent transitions to create adaptive biomaterials. When integrated with theoretical modeling, single-molecule data provide a coherent framework that links protonation dynamics to folding mechanisms across timescales. Here, in this review, we have not only consolidated current knowledge but also identified key gaps, particularly in connecting molecular-level protonation events with cellular and pathological contexts. By bridging these dimensions, this perspective aims to inspire new strategies in biomolecular engineering, therapeutic design, and the development of responsive functional materials.

蛋白质折叠和质子化是紧密相连的。可电离残基电荷状态的变化改变了局部静电和有效pKa值，影响了蛋白质如何导航其构象景观。这些质子化事件可以稳定中间体，引导折叠途径，并引入支持功能适应性的动力学多样性。因此，了解折叠-质子化耦合已成为蛋白质科学的一个主要焦点。为了探索这些复杂的动态，需要越来越复杂的方法。其中，单分子荧光（SMF）技术已经成为特别强大的工具，提供了前所未有的折叠过程与质子化耦合的分辨率。smFRET，荧光寿命分析和快速ph跳变实验等方法使观察事件的细节成为可能。它们揭示了在整体研究中未被检测到的中间产物，捕获了异质亚群，并揭示了对生物功能至关重要的罕见的瞬时事件。在这些方法学进展的基础上，几个案例研究说明了质子化如何影响生物结果，例如，富含组氨酸的结构域作为分子pH传感器，病毒融合蛋白利用质子化触发的折叠来介导宿主进入，工程生物开关利用pka依赖的转变来创造自适应生物材料。当与理论建模相结合时，单分子数据提供了一个连贯的框架，将质子化动力学与跨时间尺度的折叠机制联系起来。在这篇综述中，我们不仅巩固了现有的知识，而且还确定了关键的空白，特别是在分子水平的质子化事件与细胞和病理背景之间的联系。通过连接这些维度，这一观点旨在激发生物分子工程、治疗设计和响应功能材料开发的新策略。

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引用次数: 0

Hydration parameters (h values) of hydrophobic l-amino acids estimated using the viscosity B-coefficients and partial molar volumes, and the low sensitivity of macromolecular interactions of xanthan gum on the effect of these amino acids in water 利用粘度b系数和偏摩尔体积估算疏水l-氨基酸的水化参数（h值），以及黄原胶的大分子相互作用对这些氨基酸在水中的影响的低敏感性。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-12-04 DOI: 10.1016/j.bpc.2025.107549

Yukinori Sato

Hydration parameter h values of the hydrophobic l-amino acids (l-alanine, l-valine, l-leucine, l-isoleucine, and glycine as a reference) were estimated in water using the viscosity B-coefficients and partial molar volumes, and the food macromolecular interactions were explored in aqueous solutions at 25 °C using the apparent viscosities of macromolecular solutions (polyethylene glycol 3500, dextran T40, guar gum, locust bean gum, apple pectin, citrus pectin, sodium alginate, and xanthan gum) with l-amino acids (l-alanine, l-valine, and glycine as a reference). An increased number of hydrophobic groups were associated with viscosity B-coefficient values, the partial molar volume values, and hydration of approximately 1.4 mol of water per carbon-equivalent. When hydrophobic l-amino acids were added to food macromolecular solutions, the relationship between the apparent viscosity and amino acid molality could be expressed using linear regression lines; the slopes of these lines may reflect macromolecular interactions. Using this novel parameter, the contributions of the hydrophobicity of amino acids to macromolecular interactions can be compared. Glycine decreased and l-valine increased the apparent viscosities of almost all polyelectrolytes (i.e., pectins and alginate) in water, but the effects on nonelectrolytes were less marked (guar gum with glycine is an exception). The effects of l-alanine varied. However, these amino acids did not change the viscosity of xanthan in water, although xanthan is a polyelectrolyte. Thus, the low sensitivity of macromolecular interactions of xanthan gum on the effect of these hydrophobic l-amino acids has been demonstrated to be favorable for use as a stable food thickener.

利用粘度b系数和偏摩尔体积估算了疏水l-氨基酸（l-丙氨酸、l-缬氨酸、l-亮氨酸、l-异亮氨酸和甘氨酸作为参考）在水中的水化参数h值，并利用大分子溶液（聚乙二醇3500、葡聚糖T40、瓜尔胶、槐豆胶、苹果果胶、柑橘果胶、海藻酸钠、瓜尔瓜尔胶）的表观粘度在25°C水溶液中探索了食物大分子相互作用。和黄原胶)与l-氨基酸（l-丙氨酸，l-缬氨酸和甘氨酸作为参考）。疏水基团数量的增加与粘度b系数值、偏摩尔体积值和每碳当量约1.4 mol水的水合作用有关。在食品大分子溶液中加入疏水l-氨基酸，表观粘度与氨基酸摩尔浓度之间的关系可用线性回归曲线表示；这些线的斜率可以反映大分子的相互作用。利用这个新参数，可以比较氨基酸的疏水性对大分子相互作用的贡献。甘氨酸降低和l-缬氨酸增加几乎所有聚电解质（即果胶和海藻酸盐）在水中的表观粘度，但对非电解质的影响不太明显（瓜尔胶与甘氨酸是一个例外）。l-丙氨酸的作用各不相同。然而，这些氨基酸并没有改变黄原胶在水中的粘度，尽管黄原胶是一种聚电解质。因此，黄原胶的大分子相互作用对这些疏水l-氨基酸的影响的低敏感性已被证明有利于作为稳定的食品增稠剂使用。

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引用次数: 0

Microwave-assisted green synthesis of (Co, Gd) dual doped ZnO nanoparticles using Phyllanthus emblica extract and their applications 余甘子萃取物微波辅助绿色合成（Co, Gd）双掺杂ZnO纳米粒子及其应用

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-29 DOI: 10.1016/j.bpc.2025.107554

Nirdosh Verma , Dinesh Pathak , Kamal Jeet , Lacy Loveleen , Surendra Nimesh , Sunil Kumar , Naveen Thakur

This study reports a microwave-assisted green synthesis of cobalt and gadolinium dual doped ZnO nanoparticles using Phyllanthus emblica extract as a natural bio-stabilizer. The plant-derived phytochemicals enabled an eco-friendly process and improved nanoparticle stability. Structural, morphological, and optical analyses (TEM, XRD, SEM, EDX, UV–Vis) confirmed the successful formation of uniformly dispersed nanoparticles. The crystallite size obtained from XRD decreased from 26.59 to 20.59 nm with increasing Gd content, while TEM analysis showed slightly larger particle sizes ranging from 28.39 to 23 nm, validating the nanoscale dimensions and doping-induced size reduction. The (Co, Gd) dual doped ZnO nanoparticles exhibited strong antibacterial and antioxidant activity, demonstrating their potential to mitigate oxidative stress. Their photocatalytic efficiency was further confirmed through up to 97% degradation of Methyl Orange and Methylene Blue dyes. These combined results demonstrate that green synthesis and dual doping synergistically enhance the functional properties of ZnO nanoparticles, positioning them as promising candidates for environmental remediation, healthcare applications, sunscreen formulations, and active food packaging systems.

本研究报道了以余甘子提取物为天然生物稳定剂，微波辅助绿色合成钴和钆双掺杂ZnO纳米粒子。植物衍生的植物化学物质使生态友好的过程和提高纳米颗粒的稳定性。结构、形态和光学分析（TEM、XRD、SEM、EDX、UV-Vis）证实成功形成了均匀分散的纳米颗粒。随着Gd含量的增加，XRD得到的晶粒尺寸从26.59 nm减小到20.59 nm，而TEM分析显示晶粒尺寸略大，在28.39 ~ 23 nm之间，证实了掺杂引起的晶粒尺寸减小。（Co, Gd）双掺杂ZnO纳米颗粒表现出较强的抗菌和抗氧化活性，表明其具有减轻氧化应激的潜力。通过对甲基橙和亚甲基蓝染料高达97%的降解，进一步证实了它们的光催化效率。这些综合结果表明，绿色合成和双掺杂协同增强了ZnO纳米颗粒的功能特性，使其成为环境修复，医疗保健应用，防晒霜配方和活性食品包装系统的有希望的候选人。

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引用次数: 0

Recent developments and applications of photothermal AFM-IR in characterization of amyloids and amyloids aggregation processes: Mini-review 光热AFM-IR在淀粉样蛋白和淀粉样蛋白聚集过程表征中的最新进展和应用：综述。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-22 DOI: 10.1016/j.bpc.2025.107551

Quentin Machiels , Céline Duchateau , Jehan Waeytens

AFM-IR combinates atomic force microscopy and infrared spectroscopy to compensate the limitations of both techniques taken separately. It has been reviewed for a large application field like polymers, geology and life sciences. In biology, it is an important tool to study amyloids and protein aggregation processes. Indeed, misfolding can appear under various circumstances in the process of globular proteins folding. In the case of amyloidosis, fibrillar aggregates are deposited in intracellular inclusions or in tissues as extracellular plaques. These aggregates (oligomers or fibrils) are characterized by high β-sheet content which can be analyzed in AFM-IR thanks to specific absorption band. The main progresses and developments of this technique are summarized since its creation in 2005. The evolution of laser sources and new measurement modes has led to the development of new instruments. They are always more efficient, allowing faster analysis, a wider sample range or more sensitive in order to give more (chemical) information about the sample. An overview of the progress made in photothermal AFM-IR in characterization of amyloids and amyloid aggregation processes is also described. The tapping and resonance-enhanced contact AFM-IR are the most commonly used modes. Generally, the label-free analysis of the conformation of the oligomers and/or fibrils at micromolar concentration is described, either in an aggregation kinetic study or in analysis of fibrils in ex vivo study. The coaggregation of two amyloids is also realized using ¹³C-labeled peptide to distinguish both two spectral signatures.

AFM-IR结合了原子力显微镜和红外光谱，以弥补这两种技术单独采取的局限性。综述了它在聚合物、地质和生命科学等领域的广泛应用。在生物学中，它是研究淀粉样蛋白和蛋白质聚集过程的重要工具。事实上，在球形蛋白折叠过程中，在各种情况下都可能出现错误折叠。在淀粉样变的情况下，纤维聚集体沉积在细胞内包涵体或组织中作为细胞外斑块。这些聚集体（低聚物或原纤维）具有高β片含量的特点，由于具有特定的吸收带，可以在AFM-IR中进行分析。总结了该技术自2005年创立以来的主要进展和发展。激光源的发展和新的测量模式导致了新仪器的发展。它们总是更有效，允许更快的分析，更广泛的样品范围或更敏感，以便提供更多关于样品的（化学）信息。概述了光热AFM-IR表征淀粉样蛋白和淀粉样蛋白聚集过程的进展。轻敲和共振增强接触AFM-IR是最常用的模式。一般来说，在微摩尔浓度下对低聚物和/或原纤维的构象进行无标记分析，要么在聚集动力学研究中，要么在离体研究中对原纤维进行分析。利用13c标记肽来区分两种光谱特征也实现了两种淀粉样蛋白的共聚集。

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引用次数: 0

Novel heterocyclic hybrids of Thiophene clubbed 1,3,4-oxadiazoles targeting dihydrofolate reductase (DHFR): An in silico approach, molecular docking, ADMET studies, MM-GBSA assay and MD simulations 针对二氢叶酸还原酶（DHFR）的新型杂环噻吩棒化1,3,4-恶二唑：硅方法、分子对接、ADMET研究、MM-GBSA测定和MD模拟

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-21 DOI: 10.1016/j.bpc.2025.107553

S. Prasanth , B.C. Revanasiddappa , Venkatesh Ranjan , Durgesh Paresh Bidye , Sheshagiri R. Dixit

Nowadays Antimicrobial resistance (AMR) is considered as one of the major global concern and has become the leading confront since bacteria is continuously involved in the development of resistance against the diversified class of antimicrobial agents. Therefore, there is an urgent demand to find the new inhibitors and targets to overcome this problem. Dihydrofolate reductase (DHFR) is considered as one of the key enzyme, which plays a major role in supporting bacterial growth and hence these inhibitors were found to be highly effective therapeutic agents in combating bacterial infections. In this present study, Thiophene-clubbed 1,3,4-oxadiazoles derivatives (T1–15) were designed as potential DHFR inhibitors by in silico approach. We investigated 99 compounds as potential inhibitors of DHFR and the top 15 compounds were further selected for molecular docking studies. By using Schrodinger Maestro all the compounds were subjected to molecular docking study against the DHFR target (PDB:1DG5). The compounds T1 (‐8.206 kcal/mol) and T2 (−7.701 kcal/mol) exhibited highest docking scores when compared to the standard Trimethoprim (−6.482) and adhered to Lipinski rule for drug likeness, ADMET and toxicity profile. The MM-GBSA analysis indicated stable binding free energies. MD simulations have been performed for compound T1 and Trimethoprim to determine the stability of the complex for 200 ns. Overall, this research lays the groundwork in the development of novel class of DHFR inhibitors.

目前，抗生素耐药性（AMR）被认为是全球关注的主要问题之一，并已成为主要的对抗，因为细菌不断参与对各种抗微生物药物的耐药性发展。因此，迫切需要找到新的抑制剂和靶点来克服这一问题。二氢叶酸还原酶（DHFR）被认为是支持细菌生长的关键酶之一，因此这些抑制剂被发现是对抗细菌感染的高效治疗剂。在本研究中，噻吩棒状的1,3,4-恶二唑衍生物（T1-15）被设计为潜在的DHFR抑制剂。我们研究了99个化合物作为DHFR的潜在抑制剂，并进一步选择了前15个化合物进行分子对接研究。利用Schrodinger Maestro软件对所有化合物与DHFR靶点（PDB:1DG5）进行分子对接研究。化合物T1（‐8.206 kcal/mol）和T2（−7.701 kcal/mol）与标准的甲氧苄啶（−6.482 kcal/mol）相比具有最高的对接分数，并且在药物相似性、ADMET和毒性谱方面符合Lipinski规则。MM-GBSA分析表明结合自由能稳定。对化合物T1和甲氧苄啶进行了MD模拟，以确定配合物在200 ns内的稳定性。总之，本研究为开发新型DHFR抑制剂奠定了基础。

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引用次数: 0

Study of neurotransmitter dopamine interaction with DNA by electrochemical and spectroscopic methods 神经递质多巴胺与DNA相互作用的电化学和光谱研究。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-17 DOI: 10.1016/j.bpc.2025.107552

Poghos O. Vardevanyan , Gaspar H. Kocharyan , Marine A. Parsadanyan , Anna V. Vardanyan , Mariam A. Shahinyan , Ara P. Antonyan

Dopamine interaction with DNA has been studied using square-wave voltammetry (SWV), fluorescence, and absorption spectroscopy. The effect of dopamine on the binding of classical intercalating agents, such as acridine orange (AO), ethidium bromide (EtBr) as well as classical groove binding ligand Hoechst 33258 (H33258) was evaluated. The obtained results clarify the molecular mechanisms of dopamine interaction with DNA and reveal its potential competition for intercalation and minor groove binding sites which show that dopamine interacts with DNA by multimodal modes. On the basis of fluorescence measurements, the values of the binding constant (K) and the number of base pairs (n) per binding site were determined. It was revealed that the values of these binding parameters (K and n) depend on the ionic strength of the solution. Based on the changes of the binding parameters of AO, EtBr and H33258 with DNA in the absence and presence of dopamine, it was shown that the presence of the neurotransmitter reduces the affinity of these ligands toward DNA. The obtained data indicate that dopamine binds to DNA via intercalation and minor groove binding mechanisms, which leads to a decrease in the binding constants of these ligands with DNA. In the case of dopamine interaction with DNA in the presence of intercalators, the effect is especially pronounced for the strong (intercalation) binding mode of EtBr, as its binding constant with DNA in the presence of dopamine is significantly lower than that of AO.

利用方波伏安法（SWV）、荧光和吸收光谱研究了多巴胺与DNA的相互作用。评价了多巴胺对经典插层剂如吖啶橙（AO）、溴化乙啶（EtBr）以及经典凹槽结合配体Hoechst 33258 （H33258）结合的影响。研究结果阐明了多巴胺与DNA相互作用的分子机制，揭示了多巴胺与DNA相互作用的嵌入位点和小凹槽结合位点的潜在竞争，表明多巴胺与DNA的相互作用是多模式的。根据荧光测量，确定结合常数(K)和每个结合位点的碱基对数(n)。结果表明，这些结合参数（K和n）的值取决于溶液的离子强度。基于AO、EtBr和H33258在多巴胺缺失和存在情况下与DNA结合参数的变化，表明多巴胺的存在降低了这些配体对DNA的亲和力。所获得的数据表明，多巴胺通过嵌入和小槽结合机制与DNA结合，导致这些配体与DNA的结合常数降低。在多巴胺与插入物存在的DNA相互作用的情况下，EtBr的强（插入）结合模式的影响尤其明显，因为在多巴胺存在的情况下，EtBr与DNA的结合常数明显低于AO。

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引用次数: 0

Development of an EPR-based methodology to study protein-lipid interaction 开发基于epr的方法来研究蛋白质-脂质相互作用。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-08 DOI: 10.1016/j.bpc.2025.107550

Clara Piersson , Shikhar Prakash , Victoria Lublin , Melanie Rossotti , Baptiste Fischer , Madhur Srivastava , Yann Fichou

The interaction of protein with other biomolecules is central to all cellular processes. In particular, protein-lipid interactions play an essential role in regulating soluble and membrane protein function, structure, and dynamics. However, probing these interactions remains challenging due to the complexity and heterogeneity of membranes. Various methods have been developed to characterize protein-membrane interaction, each presenting advantages and limitations. This study presents a robust methodology based on continuous-wave Electron Paramagnetic Resonance (CW-EPR) spectroscopy to characterize protein–membrane interactions. We focused on the protein Tau, an intrinsically disordered protein associated with neurodegenerative diseases. We show that the interaction of labelled Tau with lipids gives rise to a very distinct lineshape, which can be used to quantify the fraction of bound protein. This allows to obtain the apparent binding mode and affinity through titration experiments. In addition, we show that a single measurement provides the absolute concentration of free and bound protein. We argue that this information, which is rarely obtained by other methods providing relative signals, is very useful for mechanistic studies. Furthermore, we developed a minimal-data approach and demonstrated that a single EPR measurement can be used to estimate an apparent binding constant. The approach is applied to the Tau-membrane interaction occurring in different conditions affecting the binding behavior. The presented methodology is expected to be applicable to other proteins.

蛋白质与其他生物分子的相互作用是所有细胞过程的核心。特别是，蛋白质-脂质相互作用在调节可溶性和膜蛋白的功能、结构和动力学中起着至关重要的作用。然而，由于膜的复杂性和非均质性，探测这些相互作用仍然具有挑战性。已经开发了各种方法来表征蛋白质-膜相互作用，每种方法都有其优点和局限性。本研究提出了一种基于连续波电子顺磁共振（CW-EPR）光谱的稳健方法来表征蛋白质-膜相互作用。我们专注于Tau蛋白，这是一种与神经退行性疾病相关的内在紊乱蛋白。我们发现标记的Tau与脂质的相互作用产生了非常明显的线形，可以用来量化结合蛋白的比例。这样可以通过滴定实验获得表观结合模式和亲和力。此外，我们表明，一次测量提供了游离和结合蛋白的绝对浓度。我们认为，这一信息，很少得到其他方法提供相对信号，是非常有用的机制研究。此外，我们开发了一种最小数据方法，并证明了单个EPR测量可以用来估计表观结合常数。该方法应用于不同条件下影响结合行为的tau -膜相互作用。所提出的方法有望适用于其他蛋白质。

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引用次数: 0

Thermodynamics and kinetics analysis of lipid-assisted transport of intrinsically disorder proteins. 内在无序蛋白脂质辅助转运的热力学和动力学分析。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.bpc.2025.107504

Carmelo La Rosa

Intrinsically disordered proteins (IDPs) are implicated in numerous neurodegenerative diseases, including Alzheimer's, Parkinson's, and type 2 diabetes. Although the amyloid and toxic oligomer hypotheses have provided significant molecular insights into these diseases, they are incomplete in fully explaining the complexity of the observed phenomena. In this study, we propose a new quantitative hypothesis, the lipid-chaperone hypothesis, which postulates a central role for the interaction between IDPs and lipids in the pathogenesis of these diseases. The resulting lipid-protein complex facilitate protein transfer into the cell membrane and the subsequent formation of pores, compromising cellular integrity. To experimentally test this hypothesis, we developed a mathematical model describing the kinetics of pore formation. The model was calibrated using experimental data and allowed us to estimate the kinetic constants and Gibbs free energy associated with the formation of the lipid-protein complex. These results support the hypothesis that the interaction between IDPs and lipids is a crucial event in the pathogenesis of IDP-related diseases and suggest that modulating this interaction could represent a promising therapeutic strategy.

内在无序蛋白（IDPs）与许多神经退行性疾病有关，包括阿尔茨海默病、帕金森病和2型糖尿病。尽管淀粉样蛋白和毒性低聚物假说为这些疾病提供了重要的分子见解，但它们在完全解释所观察到的现象的复杂性方面是不完整的。在这项研究中，我们提出了一个新的定量假设，即脂质伴侣假说，该假说假设IDPs和脂质之间的相互作用在这些疾病的发病机制中起核心作用。由此产生的脂蛋白复合物促进蛋白质转移到细胞膜和随后形成的毛孔，损害细胞的完整性。为了实验验证这一假设，我们建立了一个描述孔隙形成动力学的数学模型。该模型使用实验数据进行校准，使我们能够估计与脂蛋白复合物形成相关的动力学常数和吉布斯自由能。这些结果支持了idp和脂质之间的相互作用是idp相关疾病发病机制中一个关键事件的假设，并表明调节这种相互作用可能代表一种有希望的治疗策略。

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