Molecular dynamics study of Cl^- permeation through cystic fibrosis transmembrane conductance regulator (CFTR).

ABSTRACT: The recent elucidation of atomistic structures of Cl^- channel CFTR provides opportunities for understanding the molecular basis of cystic fibrosis. Despite having been activated through phosphorylation and provided with ATP ligands, several near-atomistic cryo-EM structures of CFTR are in a closed state, as inferred from the lack of a continuous passage through a hydrophobic bottleneck region located in the extracellular portion of the pore. Here, we present repeated, microsecond-long molecular dynamics simulations of human CFTR solvated in a lipid bilayer and aqueous NaCl. At equilibrium, Cl^- ions enter the channel through a lateral intracellular portal and bind to two distinct cationic sites inside the channel pore but do not traverse the narrow, de-wetted bottlenec

SUBMITTER: Zeng ZW 

PROVIDER: S-EPMC9873711 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature