日本質量分析学会 第70回質量分析総合討論会会

演題概要

オーラルセッション

第1日 6月22日(水) 17:30~17:50 A会場(メインホール)

標的タンパク質同定に向けたヒスチジン重水素置換質量分析法の検討

(1田辺三菱製薬2ケース・ウェスタン・リザーブ大学)
o田中恒平1岸本太郎1渡辺心子1光井かおり1奥村千英子1村崎広太1宮城大2

It is known that binding of a ligand stabilizes proteins against chemical or heat-induced denaturation. Based on this principle, several mass spectrometry-based proteomic approaches for identifying protein-ligand interactions have been developed, such as SPROX (Stability of Proteins from Rates of Oxidation), DARTS (Drug Affinity Responsive Target Stability), CETSA (Cellular Thermal Shift Assay) and TPP (Thermal Proteome Profiling). Although these methods have shown encouraging results, identifying low abundant and multi-domain proteins is still a challenge. We foresee that histidine hydrogen-deuterium exchange mass spectrometry (His-HDX-MS), which measures the slow HDX of histidine imidazole groups in proteins using mass spectrometry, has the potential to overcome these drawbacks. Here we used His-HDX-MS as a platform to measure heat-induced unfolding of proteins and evaluated the applicability of this platform to identify protein-ligand interactions.