Agonist-induced dimer dissociation as a macromolecular step in
G protein-coupled receptor signaling

J 2017

Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling

PETERSEN, J., SC WRIGHT, D. RODRIGUEZ, P. MATRICON, N. LAHAV et. al.

Basic information

Original name

Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling

Authors

PETERSEN, J. (752 Sweden), SC WRIGHT (752 Sweden), D. RODRIGUEZ (752 Sweden), P. MATRICON (752 Sweden), N. LAHAV (376 Israel), A. VROMEN (376 Israel), A. FRIEDLER (376 Israel), J. STROMQVIST (752 Sweden), S. WENNMALM (752 Sweden), J. CARLSSON (752 Sweden) and Gunnar SCHULTE (276 Germany, guarantor, belonging to the institution)

Edition

Nature Communications, London, Nature Publishing Group, 2017, 2041-1723

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 12.353

RIV identification code

RIV/00216224:14310/17:00100420

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1038/s41467-017-00253-9

UT WoS

000407198800015

Keywords in English

CROSS-CORRELATION SPECTROSCOPY; MOLECULAR-DYNAMICS SIMULATIONS; A GPCR DIMERS; FRIZZLED 6; ADRENERGIC-RECEPTOR; CONSTANT-PRESSURE; COMPLEX; BINDING; OLIGOMERIZATION; DIMERIZATION

Abstract

V originále

G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane a-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques. Further analysis of a dimerization-impaired FZD6 mutant indicates that dimer dissociation is an integral part of FZD6 signaling to extracellular signal-regulated kinases1/2. The discovery of agonistdependent dynamics of dimers as an intrinsic process of receptor activation extends our understanding of Class F and other dimerizing GPCRs, offering novel targets for dimerinterfering small molecules.

Links

EE2.3.20.0180, research and development project

Name: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny

Citovat

PETERSEN, J., SC WRIGHT, D. RODRIGUEZ, P. MATRICON, N. LAHAV, A. VROMEN, A. FRIEDLER, J. STROMQVIST, S. WENNMALM, J. CARLSSON and Gunnar SCHULTE. Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. Nature Communications. London: Nature Publishing Group, 2017, vol. 8, August, p. 1-15. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-017-00253-9.

@article{1411800,
   author = {Petersen, J. and Wright, SC and Rodriguez, D. and Matricon, P. and Lahav, N. and Vromen, A. and Friedler, A. and Stromqvist, J. and Wennmalm, S. and Carlsson, J. and Schulte, Gunnar},
   article_location = {London},
   article_number = {August},
   doi = {http://dx.doi.org/10.1038/s41467-017-00253-9},
   keywords = {CROSS-CORRELATION SPECTROSCOPY; MOLECULAR-DYNAMICS SIMULATIONS; A GPCR DIMERS; FRIZZLED 6; ADRENERGIC-RECEPTOR; CONSTANT-PRESSURE; COMPLEX; BINDING; OLIGOMERIZATION; DIMERIZATION},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling},
   volume = {8},
   year = {2017}
}

TY  - JOUR
ID  - 1411800
AU  - Petersen, J. - Wright, SC - Rodriguez, D. - Matricon, P. - Lahav, N. - Vromen, A. - Friedler, A. - Stromqvist, J. - Wennmalm, S. - Carlsson, J. - Schulte, Gunnar
PY  - 2017
TI  - Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling
JF  - Nature Communications
VL  - 8
IS  - August
SP  - 1-15
EP  - 1-15
PB  - Nature Publishing Group
SN  - 20411723
KW  - CROSS-CORRELATION SPECTROSCOPY
KW  - MOLECULAR-DYNAMICS SIMULATIONS
KW  - A GPCR DIMERS
KW  - FRIZZLED 6
KW  - ADRENERGIC-RECEPTOR
KW  - CONSTANT-PRESSURE
KW  - COMPLEX
KW  - BINDING
KW  - OLIGOMERIZATION
KW  - DIMERIZATION
N2  - G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane a-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques. Further analysis of a dimerization-impaired FZD6 mutant indicates that dimer dissociation is an integral part of FZD6 signaling to extracellular signal-regulated kinases1/2. The discovery of agonistdependent dynamics of dimers as an intrinsic process of receptor activation extends our understanding of Class F and other dimerizing GPCRs, offering novel targets for dimerinterfering small molecules.
ER  -

PETERSEN, J., SC WRIGHT, D. RODRIGUEZ, P. MATRICON, N. LAHAV, A. VROMEN, A. FRIEDLER, J. STROMQVIST, S. WENNMALM, J. CARLSSON and Gunnar SCHULTE. Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. \textit{Nature Communications}. London: Nature Publishing Group, 2017, vol.~8, August, p.~1-15. ISSN~2041-1723. Available from: https://dx.doi.org/10.1038/s41467-017-00253-9.

Detailed Information on Publication Record