The low density lipoprotein receptor active conformation of apolipoprotein E. Helix organization in n-terminal domain-phospholipid disc particles

• Published in: The Journal of biological chemistry Vol. 273; no. 40; pp. 25825 - 25830
• Main Authors: Raussens, V, Fisher, C A, Goormaghtigh, E, Ryan, R O, Ruysschaert, J M
• Format: Journal Article
• Language: English
• Published: United States 02.10.1998
• Subjects: Apolipoprotein E3; Apolipoproteins E - chemistry; Binding Sites - physiology; Circular Dichroism; Dimyristoylphosphatidylcholine - chemistry; Models, Molecular; Protein Conformation; Protein Structure, Secondary; Receptors, LDL - metabolism; Recombinant Proteins - chemistry; Spectroscopy, Fourier Transform Infrared
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.40.25825

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