title: The low density lipoprotein receptor active conformation of apolipoprotein E. Helix organization in n-terminal domain-phospholipid disc particles.
abstract: 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.
authors.affiliation: Laboratoire de Chimie Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles CP 206/2, bd. du Triomphe, B-1050 Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Raussens
authors.forename: C A
authors.initials: CA
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Goormaghtigh
authors.forename: R O
authors.initials: RO
authors.lastname: Ryan
authors.forename: J M
authors.initials: JM
authors.lastname: Ruysschaert
mesh_terms: D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000737:chemistry*; D001665:Binding Sites / Q000502:physiology; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011973:Receptors, LDL / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D011973:Receptors, LDL; D011994:Recombinant Proteins; D004134:Dimyristoylphosphatidylcholine