AI Article Synopsis
- - The study focuses on how pentameric ligand-gated ion channels (pLGICs), which help in synaptic transmission, are influenced by their surrounding lipid environment, especially phospholipids.
- - Researchers highlight the positive modulation of the ELIC channel by the anionic phospholipid, phosphatidylglycerol, discovering that it binds uniquely when the channel is in an open state.
- - Through structural analysis and calculations, the study suggests that phosphatidylglycerol stabilizes the open state of the ELIC channel, providing insight into the molecular mechanisms of lipid modulation in pLGICs.
Article Abstract
Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668969 | PMC |
| http://dx.doi.org/10.1038/s41467-022-34813-5 | DOI Listing |
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