Folding of the apolipoprotein A1 driven by the salt concentration as a possible mechanism to improve cholesterol trapping

TL;DR

This study uses molecular dynamics simulations to explore how salt concentration influences the folding of apolipoprotein A1, potentially enhancing its ability to trap cholesterol by adopting specific conformations.

Contribution

It provides atomistic insights into salt-dependent conformational changes of apolipoprotein A1 relevant for cholesterol trapping mechanisms.

Findings

Two main conformations identified: extended and looped structures.

Looped structures may facilitate cholesterol and fatty acid association.

Salt concentration influences the prevalence of these conformations.

Abstract

The folding of the cholesterol trapping apolipoprotein A1 in aqueous solution at increasing ionic strength is studied using atomically detailed molecular dynamics simulations. We calculate various structural properties to characterize the conformation of the protein, such as the radius of gyration, the radial distribution function and the end to end distance. Additionally we report information using tools specifically tailored for the characterization of proteins, such as the mean smallest distance matrix and the Ramachandran plot. We find that two qualitatively different configurations of this protein are preferred, one where the protein is extended, and one where it forms loops or closed structures. It is argued that the latter promote the association of the protein with cholesterol and other fatty acids.