Oleic Acid Could Act as a Channel Blocker in the Inhibition of nAChR: Insights from Molecular Dynamics Simulations.

Autor:	Obiol DJ; Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Avenida Leandro N. Alem 1253, B8000CPB Bahía Blanca, Argentina., Amundarain MJ; 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., Zamarreño F; Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Avenida Leandro N. Alem 1253, B8000CPB Bahía Blanca, Argentina., Vietri A; Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Avenida Leandro N. Alem 1253, B8000CPB Bahía Blanca, Argentina., Antollini SS; Instituto de Investigaciones Bioquímicas de Bahía Blanca CONICET-UNS, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, B8000FWB Bahía Blanca, Argentina., Costabel MD; Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Avenida Leandro N. Alem 1253, B8000CPB Bahía Blanca, Argentina.
Jazyk:	angličtina
Zdroj:	The journal of physical chemistry. B [J Phys Chem B] 2024 Mar 14; Vol. 128 (10), pp. 2398-2411. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1021/acs.jpcb.3c07067
Abstrakt:	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 cis -18:1ω-9 FFA were located at the interface between the transmembrane segments of α 2 and γ subunits diffused into the channel lumen with the consequent potential ability to block the channel to the passage of ions.
Databáze:	MEDLINE
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