Membrane cholesterol access into a G-protein-coupled receptor

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Membrane cholesterol access into a G-protein-coupled receptor

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Membrane cholesterol access into a G-protein-coupled receptor

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

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

Feb 21

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000394499200001

EID výsledku v databázi Scopus

2-s2.0-85013391445