Learnings from Protein Folding Projected onto Amyloid Misfolding.
Learnings from Protein Folding Projected onto Amyloid Misfolding.
复制标题
从蛋白质折叠中学到的知识投射到淀粉样蛋白错误折叠上。
作者：
Sreeprasad T. Sreenivasan;M. Narayan
20 世纪 90 年代，我们对含二硫键蛋白质和纯构象文件夹的蛋白质折叠途径的理解发生了革命。通过创新的实验设计，高分辨率的折叠轨迹图揭示了多种中间体的存在、它们的形成和消耗，以及它们之间导致折叠蛋白质从未折叠状态形成的相互作用网络。迄今为止，就朊病毒样蛋白的淀粉样蛋白聚集途径而言，同样程度的细节仍然难以捉摸。然而，最近的一项进展导致淀粉样蛋白生成轨迹中的中间体得到解决，而不需要对其进行分离，这可能不仅会增进我们对指导淀粉样蛋白错误折叠的原子和分子水平相互作用的基本理解，而且还会影响对其相关病理学的干预努力。
The 1990s saw a revolution in our understanding of the protein folding pathways of both disulfide-bond-containing proteins and purely conformational folders. High-resolution maps of the folding trajectories, made possible by innovative experimental design, revealed the presence of multiple intermediates, their formation and consumption, and the network of interactions between them that lead to the formation of the folded protein from its unfolded state. The same level of detail has heretofore remained elusive as far as the amyloid aggregation pathways of prion-like proteins are concerned. Nevertheless, a recent development that led to the resolution of intermediates in amyloidogenic trajectories, without resort to their separation, is likely to not only advance our basic understanding of the atomic- and molecular-level interactions guiding amyloid misfolding but also impact interventional efforts in their associated pathologies.