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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F17%3A00100420" target="_blank" >RIV/00216224:14310/17:00100420 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41467-017-00253-9" target="_blank" >http://dx.doi.org/10.1038/s41467-017-00253-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-00253-9" target="_blank" >10.1038/s41467-017-00253-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EE2.3.20.0180" target="_blank" >EE2.3.20.0180: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

1-15

Kód UT WoS článku

000407198800015

EID výsledku v databázi Scopus

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