Cholesterol differentially modulates the activity of opioid and muscarinic receptors via a common binding site
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F25%3A00639092" target="_blank" >RIV/67985823:_____/25:00639092 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.bcp.2025.117296" target="_blank" >https://doi.org/10.1016/j.bcp.2025.117296</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2025.117296" target="_blank" >10.1016/j.bcp.2025.117296</a>
Alternative languages
Result language
angličtina
Original language name
Cholesterol differentially modulates the activity of opioid and muscarinic receptors via a common binding site
Original language description
G protein-coupled receptors (GPCRs) are membrane proteins that represent the largest and most therapeutically targeted receptor class, accounting for 30% of currently marketed drugs. Two binding motifs for membrane cholesterol, the cholesterol recognition amino acid consensus (CRAC) domain and the cholesterol consensus motif (CCM), have been postulated. Using a simulation of the molecular dynamics of cholesterol association with the receptor, we predicted the binding of membrane cholesterol to non-canonical sites, distinct from CRAC and CCM, at muscarinic and opioid receptors. We identified a binding site common to muscarinic and opioid receptors at TM6, with arginine 6.35 as the major residue. Membrane cholesterol depletion mimics the effects of R6.35 mutations, confirming its role in receptor modulation. Targeting cholesterol-binding sites offers novel pharmacotherapeutic strategies, including tissue-specific sterol-based modulation.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Pharmacology
ISSN
0006-2952
e-ISSN
1873-2968
Volume of the periodical
242
Issue of the periodical within the volume
Pt1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
117296
UT code for WoS article
001565629700002
EID of the result in the Scopus database
2-s2.0-105014757680