第21回日本蛋白質科学会年会

講演情報

ポスター賞フラッシュトーク

[2FT-2] プロテオーム・蛋白質工学 (2P-62~2P-87)

2021年6月17日(木) 14:00 〜 14:30 チャンネル2

座長:本田 真也(産業技術総合研究所)、長門石 曉(東京大学)

[2P-82*] Rational design of inhibitors targeting the interaction between interleukin-33 and its receptor ST2

寺西 美月1, 林 勇樹1, 新井 宗仁1,2 (1.東大・総合文化・生命環境, 2.東大・理・物理)

Allergic diseases remain a serious health problem. This study aims to design a new protein that inhibits the protein-protein interaction (PPI) between interleukin-33 (IL-33) and its receptor ST2, which is responsible for allergic diseases. ST2 has two binding surfaces, and allergic reactions are induced when both interact with each of the two sides of IL-33. Therefore, an IL-33 mutant that enhances binding on one surface but fails to bind on the other surface is expected to inhibit the IL-33/ST2 interaction. Here, we attempted to theoretically design the IL-33 mutants with enhanced affinity to ST2 on one surface. We calculated the binding energies of various IL-33 mutants to ST2 using the protein design software Rosetta and obtained six mutants that are predicted to remarkably enhance the binding to ST2. The IL-33 proteins with a cysteine inserted at the N-terminal region were prepared, and fluorescein was attached at the Cys residue as a fluorescent label. The dissociation constant was measured by the IL-33 titration with ST2 using fluorescence anisotropy. The detailed results will be presented at the meeting.