Abstract
Apolipoprotein A-I (apoA-I) is the principal protein of high density lipoprotein particles (HDL). ApoA-I contains a globular N-terminal domain (residues 1-43) and a lipid-binding C-terminal domain (residues 44-243). Here we propose a detailed model for the smallest discoidal HDL, consisting of two apoA-I molecules wrapped beltwise around a small patch of bilayer containing 160 lipid molecules. The C-terminal domain of each monomer is ringlike, a curved, planar amphipathic alpha helix with an average of 3.67 residues per turn, and with the hydrophobic surface curved toward the lipids. We have explored all possible geometries for forming the dimer of stacked rings, subject to the hypothesis that the optimal geometry will maximize intermolecular salt bridge interactions. The resulting model is an antiparallel arrangement with an alignment matching that of the (nonplanar) crystal structure of lipid-free apoA-I.
Highlights
ApoA-I is an integral component of both spheroidal circulating high density lipoprotein particles (HDL) particles and the geometrically simpler discoidal nascent HDL particles
Amphipathic Helical Ring—Fig. 1A is a continuous ␣ helical net display of tandem helices 1–10 of Apolipoprotein A-I (apoA-I) plotted with the pitch of an idealized ␣ helix, 3.6 (18/5) residues per turn; the hydrophobic face of helices 1–10 forms one complete turn of a
A continuous ␣ helical net display of tandem repeats 1–10 plotted with a pitch of 3 turns per 11 residues, suggested by the 22-mer/11-mer tandem periodicity, creates a 198-residue ␣ helix with a straight hydrophobic face (Fig. 1B)
Summary
ApoA-I is an integral component of both spheroidal circulating HDL particles and the geometrically simpler discoidal (hockey puck-like) nascent HDL particles. In the recently published x-ray structure, residues 44 –243 of apoA-I form an almost continuous amphipathic ␣ helix, and the authors suggest that these results support the double belt model for discoidal HDL [7].
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