8ON7

FMRFa-bound Malacoceros FaNaC1 in lipid nanodiscs

8ON7 の概要

• エントリーDOI: 10.2210/pdb8on7/pdb
• 関連するPDBエントリー: 8ON8 8ON9 8ONA
• EMDBエントリー: 16981
• 分子名称: FMRFamide-gated sodium channel 1 (FaNaC1), FMRFamide, neuropeptide, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: neuropeptide, ion channel, deg/enac, membrane protein
• 由来する生物種: Malacoceros fuliginosus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 212151.07

構造登録者

Kalienkova, V.,Dandamudi, M.,Paulino, C.,Lynagh, T. (登録日: 2023-04-01, 公開日: 2024-02-14, 最終更新日: 2024-10-23)

主引用文献

Kalienkova, V.,Dandamudi, M.,Paulino, C.,Lynagh, T.
Structural basis for excitatory neuropeptide signaling.
Nat.Struct.Mol.Biol., 31:717-726, 2024

PubMed Abstract: 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.

PubMed: 38337033
DOI: 10.1038/s41594-023-01198-y

実験手法

ELECTRON MICROSCOPY (2.5 Å)