The Mass Spectrometry society of Japan - The 68th Annual Conference on Mass Spectrometry, Japan
Japanese

Abstract

Table of contents

Timetable

Plenary Lectures

Award Lecture

Oral Sessions (Day1, Day2, Day3)

Poster Presentations (Day1, Day2, Day3)

Panel Discussion

Luncheon Seminars (Day1, Day2, Day3)

Corporate Program

Poster Presentations

Day 1, June 22（Wed.）　　Room P (501, 502 and 503)

1P-36　　PDF

Native mass spectrometry to screen agonists and antagonists of G protein-coupled receptors (GPCRs)

(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 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.