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bioRxiv · 10.1101/2020.09.14.296392

Computationally Grafting An IgE Epitope Onto A Scaffold

Sabban, S. S.
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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, such as the protein cupin in peanuts. The immune pathway concerned with developing allergy is the Th2 immune pathway where the IgE antibody (targeting innocuous substances) binds to its Fc{varepsilon}RI receptor on Mast and Basophil cells. Currently, there is not a permanent treatment for allergies. This paper discusses a strategy and 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 antibodiess Fc{varepsilon}RI receptors 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 motif and it was excised and grafted onto a Staphylococcus aureus protein (PDB ID 1YN3). The new structures (motif + scaffold) had their sequences re-designed around the motif to find an amino acid sequence that would fold to the designed structures correctly. These ten computationally designed proteins showed successful folding when simulated using Rosettas 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 by guiding the immune system towards developing antibodies against the bodys own IgE antibody, thus neutralising it, and presumably permanently shutting down a major aspect of the Th2 immune pathway. This work employed in silico based methods for designing the proteins and did not include any experimental verifications.

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Sabban, S. S.. 2020-09-15. Computationally Grafting An IgE Epitope Onto A Scaffold. https://doi.org/10.1101/2020.09.14.296392

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