Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F05%3A00026212" target="_blank" >RIV/68378041:_____/05:00026212 - isvavai.cz</a>
Result on the web
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DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR
Original language description
G-protein-coupled receptors (GPCRs) have been shown to form dimers, but the relevance of this phenomenon in G-protein activation is not known. Among the large GPCR family, metabotropic glutamate (mGlu) receptors are constitutive dimers. Here we examinedwhether both heptahelical domains (HDs) are turned on upon full receptor activation. We show that a mutation in the third intracellular loop (i3 loop) known to prevent G-protein activation in a single subunit decreases coupling efficacy. However, when asingle HD is blocked in its inactive state using an inverse agonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), no decrease in receptor activity is observed. Interestingly, in a receptor dimer in which the subunit that binds MPEP is mutated in its i3 loop, MPEP enhances agonist-induced activity, reflecting a 'better' activation of the adjacent HD.
Czech name
Evidence pro aktivaci jedné transmembránové domény v dimerickém receptoru spřeženém s G-proteiny
Czech description
Popisujeme aktivaci metabotropních glutamátových receptorů, které existují na povrchu buněk jako podvojné struktury složené ze dvou identických podjednotek kovalentně spojených v extracelulární části. Naše výsledky jasně dokazují, že v aktivovaném receptoru je schopná dosáhnout aktivního stavu vždy pouze jedna podjednotka, respektive její transmemrábnová heptahelikální doména, jejíž nitrobuněčné části dále aktivují spřažené G-proteiny.
Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2005
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Journal
ISSN
0261-4189
e-ISSN
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Volume of the periodical
24
Issue of the periodical within the volume
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Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
499-509
UT code for WoS article
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EID of the result in the Scopus database
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