Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EE2.3.20.0180" target="_blank" >EE2.3.20.0180: Cooperation between Masaryk University and Karolinska Institutet, Stockholm in the field of biomedicine</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
August
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
1-15
UT code for WoS article
000407198800015
EID of the result in the Scopus database
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