Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00507094" target="_blank" >RIV/61388963:_____/19:00507094 - isvavai.cz</a>
Výsledek na webu
<a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007033" target="_blank" >https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007033</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pcbi.1007033" target="_blank" >10.1371/journal.pcbi.1007033</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions
Popis výsledku v původním jazyce
G protein-coupled receptors (GPCRs) control cellular signaling and responses. Many of these GPCRs are modulated by cholesterol and polyunsaturated fatty acids (PUFAs) which have been shown to co-exist with saturated lipids in ordered membrane domains. However, the lipid compositions of such domains extracted from the brain cortex tissue of individuals suffering from GPCR-associated neurological disorders show drastically lowered levels of PUFAs. Here, using free energy techniques and multiscale simulations of numerous membrane proteins, we show that the presence of the PUFA DHA helps helical multi-pass proteins such as GPCRs partition into ordered membrane domains. The mechanism is based on hybrid lipids, whose PUFA chains coat the rough protein surface, while the saturated chains face the raft environment, thus minimizing perturbations therein. Our findings suggest that the reduction of GPCR partitioning to their native ordered environments due to PUFA depletion might affect the function of these receptors in numerous neurodegenerative diseases, where the membrane PUFA levels in the brain are decreased. We hope that this work inspires experimental studies on the connection between membrane PUFA levels and GPCR signaling.
Název v anglickém jazyce
Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions
Popis výsledku anglicky
G protein-coupled receptors (GPCRs) control cellular signaling and responses. Many of these GPCRs are modulated by cholesterol and polyunsaturated fatty acids (PUFAs) which have been shown to co-exist with saturated lipids in ordered membrane domains. However, the lipid compositions of such domains extracted from the brain cortex tissue of individuals suffering from GPCR-associated neurological disorders show drastically lowered levels of PUFAs. Here, using free energy techniques and multiscale simulations of numerous membrane proteins, we show that the presence of the PUFA DHA helps helical multi-pass proteins such as GPCRs partition into ordered membrane domains. The mechanism is based on hybrid lipids, whose PUFA chains coat the rough protein surface, while the saturated chains face the raft environment, thus minimizing perturbations therein. Our findings suggest that the reduction of GPCR partitioning to their native ordered environments due to PUFA depletion might affect the function of these receptors in numerous neurodegenerative diseases, where the membrane PUFA levels in the brain are decreased. We hope that this work inspires experimental studies on the connection between membrane PUFA levels and GPCR signaling.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2019
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
PLoS Computational Biology
ISSN
1553-7358
e-ISSN
—
Svazek periodika
15
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
16
Strana od-do
e1007033
Kód UT WoS článku
000471040500052
EID výsledku v databázi Scopus
2-s2.0-85066964975