Sabban Sari S
King Abdulaziz University, Faculty of Science, Department of Biological Sciences, Jeddah, Saudi Arabia.
Comput Struct Biotechnol J. 2021 Aug 14;19:4738-4750. doi: 10.1016/j.csbj.2021.08.012. eCollection 2021.
Allergy is becoming an intensifying disease among the world population, particularly in the developed world. Once allergy develops, sufferers are permanently trapped in a hyper-immune response that makes them sensitive to innocuous substances. The immune pathway concerned with developing allergy is the Th immune pathway where the IgE antibody binds to its Fc RI receptor on Mast and Basophil cells. This paper discusses a protocol that could disrupt the binding between the antibody and its receptor for a potential permanent treatment. Ten proteins were computationally designed to display a human IgE motif very close in proximity to the IgE antibody's Fc RI receptor's binding site in an effort for these proteins to be used as a vaccine against our own IgE antibody. The motif of interest was the FG loop motif and it was excised and grafted onto a protein (PDB ID 1YN3), then the motif + scaffold structure had its sequence re-designed around the motif to find an amino acid sequence that would fold to the designed structure correctly. These ten computationally designed proteins showed successful folding when simulated using Rosetta's AbinitioRelax folding simulation and the IgE epitope was clearly displayed in its native three-dimensional structure in all of them. These designed proteins have the potential to be used as a pan anti-allergy vaccine. This work employed
过敏在世界人口中已成为一种日益严重的疾病，尤其是在发达国家。一旦过敏发生，患者就会永久陷入一种超免疫反应中，使他们对无害物质敏感。与过敏发生相关的免疫途径是Th免疫途径，其中IgE抗体与其在肥大细胞和嗜碱性粒细胞上的Fc RI受体结合。本文讨论了一种方案，该方案可能会破坏抗体与其受体之间的结合，从而实现潜在的永久治疗。通过计算机设计了十种蛋白质，使其呈现出与IgE抗体的Fc RI受体结合位点非常接近的人IgE基序，以便将这些蛋白质用作针对我们自身IgE抗体的疫苗。感兴趣的基序是FG环基序，将其切除并嫁接到一种蛋白质（PDB ID 1YN3）上，然后围绕该基序对基序 + 支架结构的序列进行重新设计，以找到能够正确折叠成设计结构的氨基酸序列。当使用Rosetta的从头开始松弛折叠模拟进行模拟时，这十种通过计算机设计的蛋白质显示出成功折叠，并且在所有蛋白质中IgE表位均以其天然三维结构清晰显示。这些设计的蛋白质有潜力用作泛抗过敏疫苗。这项工作采用了
