Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Avenida Leandro N. Alem 1253, B8000CPB Bahía Blanca, Argentina.
Department of Chemistry, Organic Chemistry III, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany.
J Phys Chem B. 2024 Mar 14;128(10):2398-2411. doi: 10.1021/acs.jpcb.3c07067. Epub 2024 Mar 6.
The activation of the muscular nicotinic acetylcholine receptor (nAChR) produces the opening of the channel, with the consequent increase in the permeability of cations, triggering an excitatory signal. Free fatty acids (FFA) are known to modulate the activity of the receptor as noncompetitive antagonists, acting at the membrane-AChR interface. We present molecular dynamics simulations of a model of nAChR in a desensitized closed state embedded in a lipid bilayer in which distinct membrane phospholipids were replaced by two different monounsaturated FFA that differ in the position of a double bond. This allowed us to detect and describe that the -18:1ω-9 FFA were located at the interface between the transmembrane segments of α and γ subunits diffused into the channel lumen with the consequent potential ability to block the channel to the passage of ions.
肌肉烟碱型乙酰胆碱受体 (nAChR) 的激活会导致通道打开，继而增加阳离子的通透性，引发兴奋信号。已知游离脂肪酸 (FFA) 作为非竞争性拮抗剂调节受体的活性，作用于膜-AChR 界面。我们展示了嵌入双层脂膜中的失敏关闭状态 nAChR 模型的分子动力学模拟，其中不同的膜磷脂被两种不同位置双键不同的单不饱和 FFA 取代。这使我们能够检测和描述 -18:1ω-9 FFA 位于 α 和 γ 亚基跨膜片段之间的界面上，扩散到通道腔中，从而有可能阻止离子通过通道。
