Membrane cholesterol access into a G-protein-coupled receptor
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00474932" target="_blank" >RIV/61388963:_____/17:00474932 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/ncomms14505" target="_blank" >https://www.nature.com/articles/ncomms14505</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/ncomms14505" target="_blank" >10.1038/ncomms14505</a>
Alternative languages
Result language
angličtina
Original language name
Membrane cholesterol access into a G-protein-coupled receptor
Original language description
Cholesterol is a key component of cell membranes with a proven modulatory role on the function and ligand-binding properties of G-protein-coupled receptors (GPCRs). Crystal structures of prototypical GPCRs such as the adenosine A(2A) receptor (A(2A)R) have confirmed that cholesterol finds stable binding sites at the receptor surface suggesting an allosteric role of this lipid. Here we combine experimental and computational approaches to show that cholesterol can spontaneously enter the A(2A)R-binding pocket from the membrane milieu using the same portal gate previously suggested for opsin ligands. We confirm the presence of cholesterol inside the receptor by chemical modification of the A(2A)R interior in a biotinylation assay. Overall, we show that cholesterol's impact on A(2A)R-binding affinity goes beyond pure allosteric modulation and unveils a new interaction mode between cholesterol and the A(2A)R that could potentially apply to other GPCRs.
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
10403 - Physical chemistry
Result continuities
Project
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Continuities
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
Feb 21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
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UT code for WoS article
000394499200001
EID of the result in the Scopus database
2-s2.0-85013391445