Direct Visualization of the Dynamic Process of Epsilon Toxin on Hemolysis
Direct Visualization of the Dynamic Process of Epsilon Toxin on Hemolysis
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DOI：
10.1002/smtd.202300028
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发表时间：
2023-04
期刊：
影响因子：
12.4
通讯作者：
Bin Ji;Jianxiang Huang;Kexuan Zou;M. Liu;Yufeng Pei;Jing Huang;Yong Wang;Jinglin Wang
中科院分区：
文献类型：
--
作者：
Bin Ji;Jianxiang Huang;Kexuan Zou;M. Liu;Yufeng Pei;Jing Huang;Yong Wang;Jinglin Wang
溶血是通过使用溶血素在其膜上形成纳米孔而使红细胞（红血细胞）破裂的过程，所述纳米孔然后阻碍膜渗透性。然而，在跨膜孔状态之前的自组装过程和构象变化的潜在机制尚未完全理解。在这项工作中，产气荚膜梭菌毒素（ETX），一种典型的溶血素，前孔形态的理论和实验证据，使用原位原子力显微镜（AFM）补充分子动力学（MD）模拟检测云母中不同状态的构象分布。AFM表明ETX孔的形成分为两个阶段：ETX单体首先附着在膜上并在不需要特殊条件的情况下形成预孔，然后在受体存在的情况下，在高于临界点的温度下进行构象变化以形成跨膜孔。作者的分子动力学模拟表明，当特定的氨基酸吸附到带负电荷的云母空腔时，会发生初始成核。这项工作填补了理解溶血的早期阶段和溶血素寡聚化的知识空白。此外，新鉴定的ETX前孔有望成为纳米孔应用的候选者。
Hemolysis is the process of rupturing erythrocytes (red blood cells) by forming nanopores on their membranes using hemolysins, which then impede membrane permeability. However, the self‐assembly process before the state of transmembrane pores and underlying mechanisms of conformational change are not fully understood. In this work, theoretical and experimental evidence of the pre‐pore morphology of Clostridium perfringens epsilon toxin (ETX), a typical hemolysin, is provided using in situ atomic force microscopy (AFM) complemented by molecular dynamics (MD) simulations to detect the conformational distribution of different states in Mica. The AFM suggests that the ETX pore is formed in two stages: ETX monomers first attach to the membrane and form a pre‐pore in no special conditions required, which then undergo a conformational change to form a transmembrane pore at temperatures above the critical point in the presence of receptors. The authors’ MD simulations reveal that initial nucleation occurs when specific amino acids adsorb to negatively charged mica cavities. This work fills the knowledge gap in understanding the early stage of hemolysis and the oligomerization of hemolysins. Moreover, the newly identified pre‐pore of ETX holds promise as a candidate for nanopore applications.