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

ポスター発表

第1日 6月22日(水)  P会場(501,502,503)

Gタンパク質共役受容体(GPCR)の作動薬・拮抗薬をスクリーニングするネイティブ質量分析

(1横市大院生命医2理研3サントリー生科財団)
o田尻道子1今井駿輔2小沼剛1島本啓子3嶋田一夫2明石知子1

G protein-coupled receptors (GPCRs) are seven-transmembrane receptors responsible for many physiological processes. Although GPCRs are important drug targets because of their involvement in various diseases, screening for effective binding and activity-regulating molecules remains challenging. Native mass spectrometry (MS) has been attracting interest as a useful analytical tool for membrane proteins. However, GPCRs are structurally unstable among membrane proteins, and it is extremely difficult to observe their complexes with ligands. The β2 adrenergic receptor (β2AR) is a typical GPCR, and it is known that binding of Nanobody 80 (Nb80) or mini-GS stabilizes the active form of β2AR. In addition, the activation levels, i.e., efficacy, by the ligand binding varies depending on the ligands, and the ligand efficacy reflects to the drug potency. In this study, we successfully observed the complexes of β2AR and Nb80 or mini-GS in the presence of ligand by native MS, and examined to distinguish between agonists and antagonists and to quantitatively compare the ligand efficacy.