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bioRxiv · 10.1101/2023.02.01.526556

Aromatic amino acids in the finger domain of the FMRFamide-gated Na+ channel are involved in the FMRFamide recognition and the activation

Furukawa, Y.·Tagashira, I.
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Abstract

FMRFamide-gated Na+ channel (FaNaC) is a member of the DEG/ENaC family and activated by a neuropeptide, FMRFamide. Structural information about the FMRFamide-dependent gating is, however, still elusive. Because two phenylalanines of FMRFamide are essential for the activation of FaNaC, we hypothesized that aromatic-aromatic interaction between FaNaC and FMRFamide is critical for FMRFamide recognition and/or the activation gating. Here, we focused on eight conserved aromatic residues in the finger domain of FaNaCs and tested our hypothesis by mutagenic analysis and in silico docking simulations The mutation of conserved aromatic residues in the finger domain reduced the FMRFamide potency, the extent of which were dependent on the mutated position, suggesting that the conserved aromatic residues are more or less involved in the FMRFamide-dependent activation. The kinetics of the FMRFamide-gated currents were also modified substantially in some mutants. The docking simulations revealed the aromatic-aromatic interaction between some conserved aromatic residues in FaNaC and FMRFamide. Collectively, our results suggest that the conserved aromatic residues in the finger domain of FaNaC are important determinants of the ligand recognition and/or the activation gating in FaNaC.

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Furukawa, Y., Tagashira, I.. 2023-02-03. Aromatic amino acids in the finger domain of the FMRFamide-gated Na+ channel are involved in the FMRFamide recognition and the activation. https://doi.org/10.1101/2023.02.01.526556

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