PDF(Sci-hub)
Abstract：
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 Th2 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 Staphylococcus aureus 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 employedin silicobased methods for designing the proteins and did not include any experimental verifications.
摘要：
过敏正在成为世界人口中加剧的疾病，特别是在发达国家。一旦过敏发展，患者永久地被困在一种过度免疫反应中，使他们对无害物质敏感。与发展变态反应有关的免疫途径是Th2免疫途径,其中IgE抗体结合到肥大细胞和嗜碱性粒细胞上的FcβRI受体。本文讨论了一种可能破坏抗体与其受体之间结合的方案，以进行潜在的永久性治疗。计算设计了10种蛋白质，以显示非常接近IgE抗体的FcβRI受体结合位点的人IgE基序，以努力将这些蛋白质用作针对我们自己的IgE抗体的疫苗。感兴趣的基序是FG环基序，将其切下并移植到金黄色葡萄球菌蛋白（PDBID1YN3）上，然后，基序+支架结构在基序周围重新设计其序列，以找到可以正确折叠到设计结构的氨基酸序列。当使用Rosetta的AbinitioRelax折叠模拟进行模拟时，这十种计算设计的蛋白质显示出成功的折叠，并且在所有这些蛋白质中，IgE表位都清楚地显示在其天然三维结构中。这些设计的蛋白质具有用作泛抗过敏疫苗的潜力。这项工作采用硅基方法设计蛋白质，不包括任何实验验证。
