图 书 馆
以人类Stefin B作为模型蛋白来研究蛋白折叠和聚集Human stefin B as a model protein to study protein folding and aggregation |
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| 课程网址: | http://videolectures.net/kolokviji_zerovnik_human_stefin/ |
| 主讲教师: | Eva Žerovnik |
| 开课单位: | 约瑟夫·斯特凡学院 |
| 开课时间: | 2019-01-15 |
| 课程语种: | 英语 |
| 中文简介: |  折叠和聚集机制在大多数蛋白质中是共有的。蛋白质是折叠的还是固有的解折叠/无序的蛋白质都不同，但是，它们都在部分解折叠的中间体上聚集，并且在大多数情况下，其机理与成核和生长相符。为了了解更多的机理，我们研究了两种同源蛋白，Stefin A和B及其嵌合变异体在淀粉样蛋白纤维上的折叠和聚集。此外，我们进行了某些EPM1 Stefin B突变体的细胞研究。我们的部分研究致力于淀粉样蛋白如何在膜内形成孔的可能共同机制。到目前为止，我们检查了模型膜，结果表明，Stefin B的低聚物和原纤维从脂质囊泡中释放钙黄绿素，增加了脂质表面上的压力，并最终导致了阶跃电流。低聚物与细胞膜结合的能力与活性氧（ROS）的增加相关，并最终导致细胞死亡。我们将提出支持“淀粉样蛋白孔”假说的新颖研究，该假说假设淀粉样蛋白生成蛋白的寡聚物的行为与成孔肽相似。寡聚物可能结合各种细胞膜，甚至使它们穿孔。使用现代高分辨率显微方法，应该可以对这些低聚物（尺寸在20至200 nm之间）进行成像，并以此方式确定其详细的定位和下游过程。 |
| 课程简介: | Folding and aggregation mechanisms are in common to most proteins. Proteins differ whether they are folded or intrinsically unfolded/disordered, however, all aggregate over partially unfolded intermediates and the mechanism in most cases conforms to nucleation and growth. In order to get to know more of the mechanism, we studied folding and aggregation to amyloid fibrils of two homologous proteins, stefins A and B and their chimeric variants. Further, we performed cellular studies of certain EPM1 stefin B mutants. Part of our studies was devoted to the possible common mechanism of how amyloid proteins form pores within membranes. Thus far we checked model membranes and it was shown that oligomers and protofibrils of stefin B release calcein from lipid vesicles, increase pressure on the lipid surface, and finally lead to step-wise currents. The capacity of the oligomers to bind to cellular membranes correlates with an increase of reactive oxygen species (ROS) and leads ultimately to cell death. We will present novel studies supporting the “amyloid pore” hypothesis, which assumes that the oligomers of amyloidogenic proteins behave similarly to pore forming peptides. The oligomers likely bind various cellular membranes and even perforate them. With modern high–resolution microscopic methods it should be possible to image these oligomers (of the size between 20 and 200 nm) and in such a way determine their detailed localization and down-stream processes. |
| 关 键 词: | 人类Stefin B; 蛋白; 折叠; 聚集 |
| 课程来源: | 视频讲座网 |
| 数据采集: | 2020-07-14：csy |
| 最后编审: | 2021-04-06：nkq |
| 阅读次数: | 50 |