Structural basis for excitatory neuropeptide signaling
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...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
09 February 2024
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| In: |
Nature structural & molecular biology
Year: 2024, Volume: 31, Issue: 4, Pages: 717-726, [1-19] |
| ISSN: | 1545-9985 |
| DOI: | 10.1038/s41594-023-01198-y |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41594-023-01198-y Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41594-023-01198-y 
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| Author Notes: | Valeria Kalienkova, Mowgli Dandamudi, Cristina Paulino & Timothy Lynagh |
| Summary: | 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. |
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| Item Description: | Gesehen am 18.06.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1545-9985 |
| DOI: | 10.1038/s41594-023-01198-y |