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Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.

<div class='caption-title'>ELIC agonist responses in different lipid conditions.</div>
<div class='caption-title'>Conformational changes of pore opening.</div>
<div class='caption-title'>Outer leaflet phospholipid binding site and conformational changes associated with ELIC opening.</div>
Petroff JT, Dietzen NM, Santiago-McRae E, Deng B, Washington MS, Chen LJ, Trent Moreland K, Deng Z, Rau M, Fitzpatrick JAJ, Yuan P, Joseph TT, Hénin J, Brannigan G, Cheng WWL
OpenAccess logo Nat Commun 13 7017 (2022)
Related entries: 8d63, 8d64, 8d65, 8d67, 8vuw

Cited: 10 times
EuropePMC logo PMID: 36385237

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.

Articles - 8d66 mentioned but not cited (1)

  1. Lipid nanodisc scaffold and size alter the structure of a pentameric ligand-gated ion channel. Dalal V, Arcario MJ, Petroff JT, Tan BK, Dietzen NM, Rau MJ, Fitzpatrick JAJ, Brannigan G, Cheng WWL. Nat Commun 15 25 (2024)


Reviews citing this publication (2)

  1. A Guide to Your Desired Lipid-Asymmetric Vesicles. Krompers M, Heerklotz H. Membranes (Basel) 13 267 (2023)
  2. Alchemical Free Energy Calculations on Membrane-Associated Proteins. Papadourakis M, Sinenka H, Matricon P, Hénin J, Brannigan G, Pérez-Benito L, Pande V, van Vlijmen H, de Graaf C, Deflorian F, Tresadern G, Cecchini M, Cournia Z. J Chem Theory Comput 19 7437-7458 (2023)

Articles citing this publication (7)



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