High-density lipoprotein particles (HDLs) are transport containers in the circulatory system that receive cellular cholesterol and lipids destined for the liver and other lipoprotein particles. Because low levels of HDL-cholesterol often indicate an increased risk for cardiovascular diseases, HDL particles are considered as important pharmacological targets for therapeutic strategies. Mature spherical HDLs develop from lipid-free apolipoprotein apoA-I through the formation of intermediate discoidal HDL particles which are the primary acceptors of cellular cholesterol. Although of high biophysical and medical importance heterogeneity in density, size, shape, as well as protein and lipid composition prohibited a detailed molecular and structural description of discoidal HDL particles. Here, we present the three-dimensional solution structure of reconstituted discoidal HDL (rdHDL) particles by combining nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and transmission electron microscopy (TEM) data.
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