8ATG

Pentameric ligand-gated ion channel GLIC with bound lipids

Summary for 8ATG

• Entry DOI: 10.2210/pdb8atg/pdb
• EMDB information: 15649
• Descriptor: Proton-gated ion channel, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate (2 entities in total)
• Functional Keywords: glic, ion channel, pentameric channel, proton-gated channel, membrane protein
• Biological source: Gloeobacter violaceus
• Total number of polymer chains: 5
• Total formula weight: 200460.65

Authors

Bergh, C.,Rovsnik, U.,Howard, R.J.,Lindahl, E. (deposition date: 2022-08-23, release date: 2023-09-06, Last modification date: 2024-03-20)

Primary citation

Bergh, C.,Rovsnik, U.,Howard, R.,Lindahl, E.
Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM.
Elife, 12:-, 2024

PubMed Abstract: Ligand-gated ion channels transduce electrochemical signals in neurons and other excitable cells. Aside from canonical ligands, phospholipids are thought to bind specifically to the transmembrane domain of several ion channels. However, structural details of such lipid contacts remain elusive, partly due to limited resolution of these regions in experimental structures. Here, we discovered multiple lipid interactions in the channel GLIC by integrating cryo-electron microscopy and large-scale molecular simulations. We identified 25 bound lipids in the GLIC closed state, a conformation where none, to our knowledge, were previously known. Three lipids were associated with each subunit in the inner leaflet, including a buried interaction disrupted in mutant simulations. In the outer leaflet, two intrasubunit sites were evident in both closed and open states, while a putative intersubunit site was preferred in open-state simulations. This work offers molecular details of GLIC-lipid contacts particularly in the ill-characterized closed state, testable hypotheses for state-dependent binding, and a multidisciplinary strategy for modeling protein-lipid interactions.

PubMed: 38289224
DOI: 10.7554/eLife.86016

Experimental method

ELECTRON MICROSCOPY (2.9 Å)