8ONA

FMRFa-bound Malacoceros FaNaC1 in lipid nanodiscs in presence of diminazene

Summary for 8ONA

• Entry DOI: 10.2210/pdb8ona/pdb
• Related: 8ON7 8ON8 8ON9
• EMDB information: 16984
• Descriptor: FMRFamide-gated sodium channel 1 (FaNaC1), FMRFamide, neuropeptide, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: neuropeptide, ion channel, deg/enac, membrane protein
• Biological source: Malacoceros fuliginosus; More
• Total number of polymer chains: 6
• Total formula weight: 210931.91

Authors

Kalienkova, V.,Dandamudi, M.,Paulino, C.,Lynagh, T. (deposition date: 2023-04-01, release date: 2024-02-14, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)