Surface pressure-dependent conformation change of apolipoprotein-derived amphipathic α-helices

Matthew A Mitsche,Donald M Small

doi:10.1194/jlr.m034462

Abstract

Amphipathic α-helices (AαH) are the primary structural motif of exchangeable apolipoproteins. AαHs in exchangeable apolipoproteins adsorb, remodel, and desorb at the surface of plasma lipoproteins in response to changes in their size or composition. A triolein/water (TO/W) interface was used as a model surface to study adsorption and desorption of AαHs at a lipoprotein-like interface. We previously reported that AαH peptides spontaneously adsorb to a TO/W interface, but they only partially desorb from the surface when the excess peptide was removed from the system. This finding suggests that "exchangeable" apolipoproteins are in fact partially exchangeable and only desorb from a surface in response to compression or change in composition. Here, we develop a thermodynamic and kinetic model to describe this phenomenon based on the change in the interfacial pressure (Π) of the C-terminal 46 amino acids of apolipoprotein A-I (C46) at a TO/W interface. This model suggests that apolipoproteins have at least two interfacial conformations that are in a surface concentration and Π-dependent equilibrium. This two-state surface equilibrium model, which is based on experimental data and is consistent with dynamic changes in Π(t), provides insights into the selective metabolism and clearance of plasma lipoproteins and the process of lipoprotein remodeling.

Highlights

Amphipathic ␣-helices (A␣H) are the primary structural motif of exchangeable apolipoproteins
Mature plasma lipoproteins, such as mature-High-density lipoproteins (HDL), as well as chylomicrons, very low density lipoproteins (VLDL), and low-density lipoproteins (LDL), are emulsion-like particles that consist of a two distinct phases: a core phase and a surface phase [1]
The proteins on the surface of lipoprotein particles constitute a family of proteins called “apolipoproteins.” Apolipoproteins are surface-active molecules that function on a lipoprotein surface to both stabilize the emulsion particle and act as cofactors and ligands for numerous biological processes required for proper assembly, metabolism, and clearance of lipoprotein particles

Summary

Introduction

Amphipathic ␣-helices (A␣H) are the primary structural motif of exchangeable apolipoproteins. A␣Hs in exchangeable apolipoproteins adsorb, remodel, and desorb at the surface of plasma lipoproteins in response to changes in their size or composition. We previously reported that A␣H peptides spontaneously adsorb to a TO/W interface, but they only partially desorb from the surface when the excess peptide was removed from the system This finding suggests that “exchangeable” apolipoproteins are partially exchangeable and only desorb from a surface in response to compression or change in composition. We develop a thermodynamic and kinetic model to describe this phenomenon based on the change in the interfacial pressure (⌸) of the C-terminal 46 amino acids of apolipoprotein A-I (C46) at a TO/W interface This model suggests that apolipoproteins have at least two interfacial conformations that are in a surface concentration and ⌸-dependent equilibrium. Exchangeable apolipoproteins transfer between different types of lipoproteins in response to changes in size and lipid composition of the particles

Methods

Results

Discussion

Conclusion