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.; SC WRIGHT; D. RODRIGUEZ; P. MATRICON; N. LAHAV; A. VROMEN; A. FRIEDLER; J. STROMQVIST; S. WENNMALM; J. CARLSSON a Gunnar SCHULTE

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

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/17:00100420

Organizační jednotka

Přírodovědecká fakulta

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://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 = {https://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://doi.org/10.1038/s41467-017-00253-9.

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