The Structure of the Apolipoprotein A-I Monomer Provides Insights Into Its Oligomerisation and Lipid-binding Mechanisms

Abstract

Apolipoprotein A-I (apoA-I) plays important roles in clearing cholesterol and phospholipids from peripheral tissues, forming high-density lipoprotein (HDL). However, despite this important function, apoA-I has a propensity to form amyloid fibrils implicated in atherosclerosis and hereditary amyloidosis. Historically, structural determination of lipid-free or lipid-poor apoA-I has been difficult. Here, we obtained the crystal structure of the apoA-I monomer in complex with the antigen-binding fragment (Fab) of a monoclonal antibody. The structure reveals that the N-terminal domain (NTD, residues 1–184) of apoA-I is a compact four-helical bundle, whereas the C-terminal domain (CTD, residues 18..