产气荚膜梭菌ε毒素（ETX）在细胞膜表面自组装成七聚体复合物并伴随特异性溶人血反应。已有研究表明ETX存在多种溶血机制，但成孔七聚体与溶血之间的关系尚不清楚。预实验发现ETX可以先结合在红细胞膜表面而不致孔，高分辨AFM表征也显示ETX可在人造磷脂表面自组装成前聚体复合物。因此我们推测ETX对红细胞的成孔与产生红细胞溶血是相互独立的分子行为。本研究拟通过构建嵌合ETX分子模型组成的人工聚体复合物，利用人红细胞为模型，分别对ETX单体发生自组装聚合，寡聚体的构象改变，复合物对溶血的影响三个方面进行研究。最终阐明ETX逐步组装的分子机制，进而解释ETX组装与特异性溶血的关系。本课题的顺利实施有望清晰地展现ETX单体到成孔这一过程，鉴定影响组装和构象变化的核心因素与步骤，为ETX相关疾病提供分子模型。

Clostridium perfringens epsilon toxin (ETX) self-assembles into a heptamer complex on the surface of the cell membrane and accompanies a specific hemolysis. Previous results have shown that ETX has multiple hemolytic mechanisms, but the relationship between ETX form heptamers and hemolysis is not clear. Pilot study showed that ETX could binding to the surface of erythrocyte membrane first without pore formation, and high resolution AFM characterization showed that ETX could self-assemble into precursor complexes on the surface of artificial phospholipids. Therefore, we inferred that the pore formation and hemolysis of erythrocytes by ETX are independent molecular behaviors. In this study, we intend to construct artificial ETX oligomers composed of chimeric DNA-ETX molecular and using human erythrocytes as the main cell model to study three aspects: self-assembly polymerization of ETX monomers, conformational changes of oligomers, and the effect of complexes on hemolysis. Finally, the molecular mechanism of the gradual assembly of ETX is elucidated, and the relationship between ETX assembly and specific hemolysis is further explained. These expected findings are beneficial to clearly demonstrate the whole process from ETX monomer to transmembrane complex, identify the core factors of assembling and conformational changing, and provide molecular models for ETX-related diseases.