New insights into the determination of HDL structure by apolipoproteins: Thematic review series: high density lipoprotein structure, function, and metabolism.

摘要: Apolipoprotein (apo)A-I is the principal protein component of HDL, and because its conformational adaptability, it can stabilize all HDL subclasses. The amphipathic α-helix structural motif that enables apoA-I to achieve this functionality. In lipid-free state, helical segments unfold refold in seconds are located N-terminal two thirds molecule where they loosely packed as a dynamic, four-helix bundle. C-terminal third forms an intrinsically disordered domain mediates initial binding phospholipid surfaces, which occurs with coupled formation. lipid affinity confers detergent-like properties; solubilize vesicular phospholipids create discoidal particles diameters approximately 10 nm. Such contain segment bilayer stabilized by molecules arranged anti-parallel, double-belt conformation around edge disc, shielding hydrophobic acyl chains from exposure water. highly dynamic different sizes certain forming loops detach reversibly particle surface. flexible adapts surface spherical bending stabilizing trefoil scaffold structure. above characteristics enable partner ABCA1 mediating efflux cellular cholesterol formation heterogeneous population nascent particles. Novel insights into structure-function relationships should help reveal mechanisms subclass distribution be manipulated.