THE LOW-DENSITY-LIPOPROTEIN RECEPTOR ACTIVE CONFORMATION OF APOLIPOPROTEIN-E - HELIX ORGANIZATION IN N-TERMINAL DOMAIN-PHOSPHOLIPID DISC PARTICLES

Lipid association is a prerequisite for receptor interactions of apoli poprotein E (apoE), Disc complexes of the N-terminal 22-kDa apoE3 rece ptor binding domain and dimyristoylphosphatidylcholine display full re ceptor binding activity. Studies have been performed to characterize c onformational adaptations of the globular, lipid-free four-helix bundl e structure that culminate in stable association of its amphipathic al pha-helices with a lipid surface. Helix-lipid interactions in bilayer disc complexes can conceivably adopt two orientations: parallel or per pendicular to the phospholipid acyl chains. Evidence based on infrared dichroism, geometrical arguments, and x-ray crystallography support t he view that defined helical segments in the four-helix bundle realign upon lipid association, orienting perpendicular to the phospholipid f atty acyl chains, circumscribing the bilayer disc. Thus, it is likely that paired helical segments align in tandem, presenting a convex rece ptor-active surface.