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-Structure paper
タイトル | Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM. |
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ジャーナル・号・ページ | Elife, Vol. 12, Year 2024 |
掲載日 | 2024年1月30日 |
![]() | Cathrine Bergh / Urška Rovšnik / Rebecca Howard / Erik Lindahl / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 2.9 Å |
構造データ | EMDB-15649, PDB-8atg: |
化合物 | ![]() ChemComp-POV: |
由来 |
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![]() | MEMBRANE PROTEIN / GLIC / ion channel / pentameric channel / proton-gated channel |