Flipped binding modes for the same agonist in closely related neuropeptide-gated ion channels.

ABSTRACT: Neuropeptides are inter-cellular signaling molecules occurring throughout animals. Most neuropeptides bind and activate G-protein-coupled receptors, but some also activate ionotropic receptors (or "ligand-gated ion channels"). This is exemplified by the tetra-peptide H-Phe-Met-Arg-Phe-NH₂ (FMRFamide (FMRFa)), which activates mollusk and annelid FMRFa-gated sodium channels (FaNaCs) from the trimeric degenerin/epithelial sodium channel superfamily. Here, we explored the structure-activity relationships determining FMRFa potency at mollusk and annelid FaNaCs in the light of emerging structural data, using synthetic neuropeptide analogs, heterologous expression, and two-electrode voltage clamp. Substitutions of the FMRFa N-terminal phenylalanine residue (F1) and methionine residue (

SUBMITTER: Claereboudt EJS 

PROVIDER: S-EPMC11993918 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature