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-Structure paper
タイトル | Structural basis for excitatory neuropeptide signaling. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 4, Page 717-726, Year 2024 |
掲載日 | 2024年2月9日 |
著者 | Valeria Kalienkova / Mowgli Dandamudi / Cristina Paulino / Timothy Lynagh / |
PubMed 要旨 | Rapid signaling between neurons is mediated by ligand-gated ion channels, cell-surface proteins with an extracellular ligand-binding domain and a membrane-spanning ion channel domain. The ...Rapid signaling between neurons is mediated by ligand-gated ion channels, cell-surface proteins with an extracellular ligand-binding domain and a membrane-spanning ion channel domain. The degenerin/epithelial sodium channel (DEG/ENaC) superfamily is diverse in terms of its gating stimuli, with some DEG/ENaCs gated by neuropeptides, and others gated by pH, mechanical force or enzymatic activity. The mechanism by which ligands bind to and activate DEG/ENaCs is poorly understood. Here we dissected the structural basis for neuropeptide-gated activity of a neuropeptide-gated DEG/ENaC, FMRFamide-gated sodium channel 1 (FaNaC1) from the annelid worm Malacoceros fuliginosus, using cryo-electron microscopy. Structures of FaNaC1 in the ligand-free resting state and in several ligand-bound states reveal the ligand-binding site and capture the ligand-induced conformational changes of channel gating, which we verified with complementary mutagenesis experiments. Our results illuminate channel gating in DEG/ENaCs and offer a structural template for experimental dissection of channel pharmacology and ion conduction. |
リンク | Nat Struct Mol Biol / PubMed:38337033 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.4 - 3.0 Å |
構造データ | EMDB-16981, PDB-8on7: EMDB-16982, PDB-8on8: EMDB-16983, PDB-8on9: EMDB-16984, PDB-8ona: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | MEMBRANE PROTEIN / Neuropeptide / ion channel / DEG/ENaC |