Cholesterol effects on alpha7-nAChR embedded in POPC bilayer

VIETRI, A. ; OBIOL, D.; AMUNDARAIN, M.J.; ZAMARREÑO, F.; ANTOLLINI, S.S.; COSTABEL, M.

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels (LGIC) made upof five transmembrane glycoprotein subunits organized pseudosymmetrically around acentral pore or channel. They can adopt three main conformational states, in addition toseveral other intermediate states: a closed (C) or resting (R) state, an open (O) state thatoccurs after agonist binding, and a desensitized (D) state that occurs after the continuedpresence of the agonist. Subtle changes in the lipid environment of the nAChRs havegreat relevance in their activity, causing significant effects on human biology. Two typesof lipid positions can be identified for these lipids: annular and non-annular. Non-annularsites are in close contact with the receptor and have a low replacement rate, while theannular ones are further away, with a higher replacement rate. In this work, we use areceptor model based on a known structure (PDB: 7EKI) inserted in a lipid bilayercomposed entirely of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids.Lipids at annular sites of the membrane were replaced by cholesterols, obtaining differentlipid environments for the receptor. Atomistic Molecular Dynamics were performed for thereceptor and the membrane with various combinations of these cholesterols.Physicochemical properties of the membrane and the receptor were analyzed andcompared with the results obtained for the control system, which lacks cholesterolmolecules.