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-Structure paper
| タイトル | Cryo-EM structures of a pentameric ligand-gated ion channel in liposomes. |
|---|---|
| ジャーナル・号・ページ | Elife, Vol. 14, Year 2025 |
| 掲載日 | 2025年7月16日 |
著者 | Vikram Dalal / Brandon K Tan / Hanrui Xu / Wayland W L Cheng / ![]() |
| PubMed 要旨 | Detergents and lipid nanodiscs affect the cryo-EM structures of pentameric ligand-gated ion channels (pLGICs) including ELIC. To determine the structure of a pLGIC in a membrane environment that ...Detergents and lipid nanodiscs affect the cryo-EM structures of pentameric ligand-gated ion channels (pLGICs) including ELIC. To determine the structure of a pLGIC in a membrane environment that supports ion channel function, we performed single particle cryo-EM of ELIC in liposomes. ELIC activation and desensitization were confirmed in liposomes with a stopped-flow thallium flux assay. Using WT ELIC and a non-desensitizing mutant (ELIC5), we captured resting, activated, and desensitized structures at high resolution. In the desensitized structure, the ion conduction pore has a constriction at the 9' leucine of the pore-lining M2 helix, indicating that 9' is the desensitization gate in ELIC. The agonist-bound structures of ELIC in liposomes are distinct from those in nanodiscs. In general, the transmembrane domain is more loosely packed in liposomes compared to nanodiscs. It has been suggested that large nanodiscs are superior for supporting membrane protein function. However, ELIC localizes to the rim of large circularized nanodiscs, and structures of ELIC in large nanodiscs deviate from the liposome structures more than those in small nanodiscs. Using liposomes for cryo-EM structure determination of a pLGIC increases our confidence that the structures are snapshots of functional states. |
リンク | Elife / PubMed:40668221 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 4.3 Å |
| 構造データ | EMDB-49382, PDB-9ngc: EMDB-49383, PDB-9ngf: EMDB-49384, PDB-9ngg: EMDB-49385, PDB-9ngi: EMDB-49390, PDB-9ngq: EMDB-49391, PDB-9ngr: EMDB-49392, PDB-9ngs: EMDB-49400, PDB-9nh4: |
| 化合物 | ![]() ChemComp-3CN: ![]() ChemComp-NA: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / ELIC / ion channel / pLGIC / Structural Protein / TRANSPORT PROTEIN |
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