The Mass Spectrometry society of Japan - The 71st Annual Conference on Mass Spectrometry, Japan
Japanese

Abstract

Table of contents

Timetable

Plenary Lecture

Symposium Sessions (Day1, Day2, Day3)

Basic Sessions (Day1, Day2, Day3)

Young Researchers' Sessions (Day1, Day2, Day3)

Poster Presentations (Day1, Day2, Day3)

Special Evening Sessions

Corporate Program

Basic Sessions

Day 3, May 17（Wed.）　09:51-10:09　Room A (Special Conference Room)

3A-O-0951　　PDF

Evaluation of drug responses to G protein-coupled receptors (GPCRs) by native mass spectrometry

(1Yokohama City Univ., 2RIKEN, 3Suntory Foundation for Life Sciences)
oMichiko Tajiri1, Shunsuke Imai2, Tsuyoshi Konuma1, Keiko Shimamoto3, Ichio Shimada2, Satoko Akashi1

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 investigated the efficacy of ligands by observing the complexes of β2AR and Nb80 or mini-Gs quantitatively in the presence of ligands using native MS. It was found that there is a strong correlation between the β2AR-mini-Gs or -Nb80 complex ratios observed in mass spectra and ligand responses obtained using cell-based assays quantitatively.