Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel.
desensitization
mass spectrometry
membrane channels
molecular biophysics
none
phospholipids
structural biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 11 2019
14 11 2019
Historique:
received:
01
08
2019
accepted:
09
10
2019
entrez:
15
11
2019
pubmed:
15
11
2019
medline:
9
4
2020
Statut:
epublish
Résumé
Pentameric ligand-gated ion channels (pLGICs) are essential determinants of synaptic transmission, and are modulated by specific lipids including anionic phospholipids. The exact modulatory effect of anionic phospholipids in pLGICs and the mechanism of this effect are not well understood. Using native mass spectrometry, coarse-grained molecular dynamics simulations and functional assays, we show that the anionic phospholipid, 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), preferentially binds to and stabilizes the pLGIC, Erwinia ligand-gated ion channel (ELIC), and decreases ELIC desensitization. Mutations of five arginines located in the interfacial regions of the transmembrane domain (TMD) reduce POPG binding, and a subset of these mutations increase ELIC desensitization. In contrast, a mutation that decreases ELIC desensitization, increases POPG binding. The results support a mechanism by which POPG stabilizes the open state of ELIC relative to the desensitized state by direct binding at specific sites.
Identifiants
pubmed: 31724949
doi: 10.7554/eLife.50766
pii: 50766
pmc: PMC6855808
doi:
pii:
Substances chimiques
Ligand-Gated Ion Channels
0
Phosphatidylglycerols
0
1-palmitoyl-2-oleoylglycero-3-phosphoglycerol
81490-05-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01GM124451
Pays : United States
Organisme : NIGMS NIH HHS
ID : K08 GM126336
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124451
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41GM103422
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18POST33960309
Pays : United States
Organisme : American Heart Association
ID : 18POST33960309
Pays : International
Organisme : NIGMS NIH HHS
ID : K08GM126336
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020579
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30DK020579
Pays : United States
Organisme : Center for the Investigation of Membrane Excitability Diseases
ID : Pilot Research Grant
Pays : International
Informations de copyright
© 2019, Tong et al.
Déclaration de conflit d'intérêts
AT, JP, FH, PS, CN, LS, GB, WC No competing interests declared
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