FMRFamide门控Na[公式:参见正文]通道(FaNaC)是DEG/ENaC家族的成员,由神经肽激活,FMRFamide.有关FMRFamide依赖性门控的结构信息是,然而,仍然难以捉摸。因为FMRFamide的两种苯丙氨酸是FaNaC活化所必需的,我们假设FaNaC和FMRFamide之间的芳族-芳族相互作用对于FMRFamide识别和/或激活门控至关重要。这里,我们专注于FaNaC的指状结构域中的八个保守的芳香族残基,并通过诱变分析和计算机对接模拟测试了我们的假设。手指结构域中保守的芳香族残基的突变降低了FMRFamide的效力,这表明保守的芳香残基参与了FMRFamide依赖性的活化。在一些突变体中,FMRFamide门控电流的动力学也被显著改变。对接模拟的一些结果与FaNaC和FMRFamide中的芳族残基之间的芳族-芳族相互作用参与FMRFamide识别的假设一致。总的来说,我们的结果表明,FaNaC手指域中的保守芳族残基是FaNaC中配体识别和/或活化门控的重要决定因素。
FMRFamide-gated Na[Formula: see text] 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, suggesting that the conserved aromatic residues are involved in the FMRFamide-dependent activation. The kinetics of the FMRFamide-gated currents were also modified substantially in some mutants. Some results of docking simulations were consistent with a hypothesis that the aromatic-aromatic interaction between the aromatic residues in FaNaC and FMRFamide is involved in the FMRFamide recognition. 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.