Počet záznamů: 1
Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions
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SYSNO ASEP 0507094 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions Tvůrce(i) Javanainen, Matti (UOCHB-X) RID, ORCID
Enkavi, G. (FI)
Guixa-González, R. (ES)
Kulig, W. (FI)
Martinez-Seara, Hector (UOCHB-X) RID, ORCID
Levental, I. (US)
Vattulainen, I. (FI)Číslo článku e1007033 Zdroj.dok. PLoS Computational Biology - ISSN 1553-734X
Roč. 15, č. 5 (2019)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova lipid-protein interactions ; A2A adenosine receptor ; surface roughness Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP EF16_019/0000729 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000471040500052 EID SCOPUS 85066964975 DOI 10.1371/journal.pcbi.1007033 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2020 Elektronická adresa https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007033
Počet záznamů: 1