dc.contributor.author
Guixa-Gonzalez, Ramon
dc.contributor.author
Albasanz, Jose L.
dc.contributor.author
Rodriguez-Espigares, Ismael
dc.contributor.author
Pastor, Manuel
dc.contributor.author
Sanz, Ferran
dc.contributor.author
Marti-Solano, Maria
dc.contributor.author
Manna, Moutusi
dc.contributor.author
Martinez-Seara, Hector
dc.contributor.author
Hildebrand, Peter W.
dc.contributor.author
Martin, Mairena
dc.contributor.author
Selent, Jana
dc.date.accessioned
2018-06-08T10:51:43Z
dc.date.available
2017-04-24T09:47:24.486Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21225
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24521
dc.description.abstract
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 A2A
receptor (A2AR) 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 A2AR-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
A2AR interior in a biotinylation assay. Overall, we show that cholesterol’s
impact on A2AR-binding affinity goes beyond pure allosteric modulation and
unveils a new interaction mode between cholesterol and the A2AR that could
potentially apply to other GPCRs.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
G protein-coupled receptors
dc.subject
Membrane lipids
dc.subject
Molecular dynamics
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Membrane cholesterol access into a G-protein-coupled receptor
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Nature Communications. - 8 (2017), Artikel Nr. 14505
dcterms.bibliographicCitation.doi
10.1038/ncomms14505
dcterms.bibliographicCitation.url
http://www.nature.com/articles/ncomms14505
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000026858
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008078
dcterms.accessRights.openaire
open access