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.

Základní údaje

Originální název

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

Autoři

PETERSEN, J. (752 Švédsko), SC WRIGHT (752 Švédsko), D. RODRIGUEZ (752 Švédsko), P. MATRICON (752 Švédsko), N. LAHAV (376 Izrael), A. VROMEN (376 Izrael), A. FRIEDLER (376 Izrael), J. STROMQVIST (752 Švédsko), S. WENNMALM (752 Švédsko), J. CARLSSON (752 Švédsko) a Gunnar SCHULTE (276 Německo, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 12.353

Kód RIV

RIV/00216224:14310/17:00100420

Organizační jednotka

Přírodovědecká fakulta

DOI

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

UT WoS

000407198800015

Klíčová slova anglicky

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

Štítky

NZ, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 3. 2018 09:59, Ing. Nicole Zrilić

Anotace

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.

Návaznosti

EE2.3.20.0180, projekt VaV

Název: 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 a Gunnar SCHULTE. Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. Nature Communications. London: Nature Publishing Group, 2017, roč. 8, August, s. 1-15. ISSN 2041-1723. Dostupné z: 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 a Gunnar SCHULTE. Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. \textit{Nature Communications}. London: Nature Publishing Group, 2017, roč.~8, August, s.~1-15. ISSN~2041-1723. Dostupné z: https://dx.doi.org/10.1038/s41467-017-00253-9.

Podrobný výpis o publikaci