Pressure perturbation calorimetry of apolipoproteins in solution and in model lipoproteins.

High-density lipoproteins (HDLs) are complexes of lipids and proteins (termed apolipoproteins) that remove cell cholesterol and protect from atherosclerosis. Apolipoproteins contain amphipathic alpha-helices that have high content (> or = 1/3) and distinct distribution of charged and apolar residues, adopt molten globule-like conformations in solution, and bind to lipid surfaces. We report the first pressure perturbation calorimetry (PPC) study of apolipoproteins. In solution, the main HDL protein, apoA-I, shows relatively large volume contraction, DeltaV(unf) = -0.33%, and an apparent reduction in thermal expansivity upon unfolding, Deltaalpha(unf) < or = 0, which has not been observed in other proteins. We propose that these values are dominated by increased charged residue hydration upon alpha-helical unfolding, which may result from disruption of multiple salt bridges. At 5 degrees C, apoA-I shows large thermal expansion coefficient, alpha(5 degrees) = 15.10(-4) K(-1), that rapidly declines upon heating from 5 to 40 degrees C, alpha(40 degrees) - alpha(5 degrees) = -4.10(-4) K(-1); apolipoprotein C-I shows similar values of alpha(5 degrees) and alpha(40 degrees). These values are larger than in globular proteins. They indicate dominant effect of charged residue hydration, which may modulate functional apolipoprotein interactions with a broad range of their protein and lipid ligands. The first PPC analysis of a protein-lipid complex is reported, which focuses on the chain melting transition in model HDL containing apoA-I or apoC-I, dimyristoyl phosphatidylcholine, and 0-20% cholesterol. The results may provide new insights into volumetric properties of HDL that modulate metabolic lipoprotein remodeling during cholesterol transport.