Institute of Protein Research, Pushchino, Moscow 142290, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya st. 16/10, Moscow 117997, Russia.
Biomolecules. 2020 Feb 5;10(2):241. doi: 10.3390/biom10020241.
Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.
淀粉样结构的工程设计是蛋白质工程的新视角领域之一。研究淀粉样形成的过程有助于寻找在医学和生物技术方面对其进行管理的方法。人工功能性淀粉样原纤维的结构基础的一个有前途的候选者是 albebetin(ABB),这是一种在 O.B. Ptitsyn 的领导下设计的人工蛋白。本文研究了该蛋白的淀粉样形成的各个方面以及控制该过程的一些方法。详细描述了该蛋白从第一个非纤维状聚集体到成熟纤维和大微米级复合物的纤维形成的四个阶段。还描述了 ABB 淀粉样形成对外部条件和某些突变的依赖性。在 ABB 的两个结构相同的α-β-β基序中引入类似的点突变会导致不同的淀粉样形成动力学。表明二硫键和高 pH 值对淀粉样纤维形成的抑制作用,可用于控制该过程。这项工作的结果为进一步设计和使用基于 ABB 的淀粉样结构提供了良好的基础。