Structure of apo A-I high-density lipoproteins: a review.
Current models of high-density lipoprotein (LP) are reviewed on the basis of physicochemical protein-lipid interactions. The micellar model of LP fails to explain the transformation of micelles into disk-shaped particles and gives an indefinite number of apo A-I molecules in the surface monolayer. Micellar structure fails to explain how changes in the conformation of apoprotein affect the structure and function of high-density LP. The phospholipid bilayer encircled by apoprotein model does not explain the accepting of nonpolar cholesterol esters by high-density LP. The transformation of a bilayer phospholipid disk into a spherical structure is unclear. Since the structure and function of LP are determined by their protein chemistry, an alternative model of high-density LP as a protein-lipid disk is developed. Apo A-I bound with polar phospholipids forms a planar amphipathic disk. Phospholipids containing the more hydrophobic polyene acids are structured by apo A-I in the monolayer on the hydrophobic side of the disk. The less unsaturated polyene acids are structured by apo A-I in the multi-lamellar phase of phospholipid bilayers on the hydrophilic side of the disk. The lateral surface of the disk is formed by hydrophilic domains of apo A-I. Each apo A-I molecule forms a separate LP. Polyene fatty acids are esterified with cholesterol by lecithin-cholesterol acyltransferase on the hydrophobic side of the disk. The cholesterol-esterified polyene acids are accepted here also in association with hydrophobic groups of amino acid residues of apo A-I. Interaction with nonpolar cholesterol esters changes the conformation of apo A-I, forming a cylindrical structure from the planar protein-lipid disk. The lateral surface of the cylinder is formed by the same hydrophilic domains of apo A-I as in the disk-shaped particle. However, the alpha-helices of these domains are arranged perpendicularly to the acyl chains of the phospholipids in the disk but in parallel in the cylinder. The interaction of apo A-I protein-lipid disks by loop domains on the lateral surfaces results in the formation of large disk-shaped structures which are specific for a low-activity lecithin-cholesterol acyltransferase. The interaction of loop domains of cylindrical high-density LP produces hexagonal structures. The heterogeneity of apo A-I LP is caused by the conformation of the apoprotein which depends on the medium: the native conformation in the hydrated medium, the intermediate conformation in association with polar phospholipids, and the final conformation in association with phospholipids and nonpolar cholesterol esters. Functional features of LP depend on the conformation of apo A-I. The active and passive transport of polyene fatty acids to cells is based on the accumulation of phospholipids of different hydrophobicity on the appropriate sides of the apo A-I amphipathic disk.
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Cardiology Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
D016632:Apolipoprotein A-I / Q000737:chemistry*; D008075:Lipoproteins, HDL / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D010743:Phospholipids