Cationic Proteins Rich in Lysine Residue Trigger Formation of Non-bilayer Lipid Phases in Model and Biological Membranes: Biophysical Methods of Study.

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Membrane Biology Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI:10.1007/s00232-023-00292-y
Meiyi Li, Edward S Gasanoff
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引用次数: 0

Abstract

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.

Abstract Image

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。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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