Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel

Hanaho Kano, Yuki Toyama, Shunsuke Imai, Yuta Iwahashi, Yoko Mase, Mariko Yokogawa, Masanori Osawa, Ichio Shimada

Research output: Contribution to journalArticle

Abstract

G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.

Original languageEnglish
Article number2008
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Inwardly Rectifying Potassium Channel
G-Protein-Coupled Receptors
GTP-Binding Proteins
Chemical activation
proteins
Heterotrimeric GTP-Binding Proteins
activation
Protein Subunits
Synaptic Transmission
Carrier Proteins
Membranes
Model structures
helices
Nuclear magnetic resonance
membranes
nuclear magnetic resonance
cells
Experiments
interactions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel. / Kano, Hanaho; Toyama, Yuki; Imai, Shunsuke; Iwahashi, Yuta; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio.

In: Nature communications, Vol. 10, No. 1, 2008, 01.12.2019.

Research output: Contribution to journalArticle

Kano, Hanaho ; Toyama, Yuki ; Imai, Shunsuke ; Iwahashi, Yuta ; Mase, Yoko ; Yokogawa, Mariko ; Osawa, Masanori ; Shimada, Ichio. / Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{07028e51e9a1464d91d6ba347a3176b6,
title = "Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel",
abstract = "G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.",
author = "Hanaho Kano and Yuki Toyama and Shunsuke Imai and Yuta Iwahashi and Yoko Mase and Mariko Yokogawa and Masanori Osawa and Ichio Shimada",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-10038-x",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel

AU - Kano, Hanaho

AU - Toyama, Yuki

AU - Imai, Shunsuke

AU - Iwahashi, Yuta

AU - Mase, Yoko

AU - Yokogawa, Mariko

AU - Osawa, Masanori

AU - Shimada, Ichio

PY - 2019/12/1

Y1 - 2019/12/1

N2 - G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.

AB - G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.

UR - http://www.scopus.com/inward/record.url?scp=85065195153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065195153&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10038-x

DO - 10.1038/s41467-019-10038-x

M3 - Article

C2 - 31043612

AN - SCOPUS:85065195153

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2008

ER -