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

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JOURNAL OF MEMBRANE BIOLOGY
卷 -, 期 -, 页码 -

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SPRINGER
DOI: 10.1007/s00232-023-00292-y

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Lipid phase polymorphism; P-31-, H-1-, H-2-NMR; EPR; Luminescence spectroscopy; Differential scanning microcalorimetry; Artificial and biological membranes

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Cationic membrane-active toxins are a group of proteins found in the venom of snakes and insects, and they have pharmacological reactions including anticancer and antimicrobial effects. These toxins can alter the structure and dynamics of plasma membranes and organelle membranes, triggering non-bilayer lipid phase transitions. This observation could potentially be used to develop novel drugs for cellular energy deficiency caused by aging and diseases.
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 (P-31-, H-1-, H-2-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. [GRAPHICS]

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