McGlinchey Ryan P, Lee Jennifer C
Laboratory of Protein Conformation and Dynamics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, U.S.A.
Isr J Chem. 2017 Jul;57(7-8):613-621. doi: 10.1002/ijch.201600080. Epub 2017 Jan 19.
Amyloids are traditionally observed in the context of disease. However, there is growing momentum that these structures can serve a beneficial role where the amyloid carries out a specific function. These so called 'functional amyloids' have all the structural hallmarks of disease-associated amyloids, raising the question as to what differentiates a well-behaved benign amyloid from a lethally destructive one. Here, we review our work on the repeat domain (RPT) from Pmel17, an important functional amyloid involved in melanin biosynthesis. Particularly, we focused our attention on the unique reversible aggregation-disaggregation process of RPT that is controlled strictly by solution pH. This pH dependence of RPT amyloid formation functions as a switch to control fibril assembly and maintains the benign nature that is associated with functional amyloids.
传统上，淀粉样蛋白是在疾病背景下被观察到的。然而，越来越多的研究表明，这些结构在淀粉样蛋白发挥特定功能时可能具有有益作用。这些所谓的“功能性淀粉样蛋白”具有与疾病相关淀粉样蛋白相同的结构特征，这就引发了一个问题：良性淀粉样蛋白与具有致命破坏性的淀粉样蛋白之间的区别是什么。在这里，我们回顾了我们对Pmel17重复结构域（RPT）的研究工作，Pmel17是一种参与黑色素生物合成的重要功能性淀粉样蛋白。特别地，我们将注意力集中在RPT独特的可逆聚集-解聚过程上，该过程严格受溶液pH值控制。RPT淀粉样蛋白形成对pH值的这种依赖性起到了控制纤维组装的开关作用，并维持了与功能性淀粉样蛋白相关的良性性质。
