Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface

Yunseok Heo, Naito Ishimoto, Ye Eun Jeon, Ji Hye Yun, Mio Ohki, Yuki Anraku, Mina Sasaki, Shunsuke Kita, Hideo Fukuhara, Tatsuya Ikuta, Kouki Kawakami, Asuka Inoue, Katsumi Maenaka, Jeremy R.H. Tame, Weontae Lee, Sam Yong Park

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer's disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site. Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison between the activated GALR2 and inactive hβ2AR was used to relate galanin binding to the movements of transmembrane (TM) helices and the G-protein interface.

Original languageEnglish
Article numbere3001714
JournalPLoS Biology
Volume20
Issue number8
DOIs
Publication statusPublished - 2022 Aug

Bibliographical note

Publisher Copyright:
© 2022 Heo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences

Fingerprint

Dive into the research topics of 'Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface'. Together they form a unique fingerprint.

Cite this