title: The C-terminal domain of apolipoprotein A-I contains a lipid-sensitive conformational trigger.
abstract: Exchangeable apolipoproteins can convert between lipid-free and lipid-associated states. The C-terminal domain of human apolipoprotein A-I (apoA-I) plays a role in both lipid binding and self-association. Site-directed spin-label electron paramagnetic resonance spectroscopy was used to examine the structure of the apoA-I C terminus in lipid-free and lipid-associated states. Nitroxide spin-labels positioned at defined locations throughout the C terminus were used to define discrete secondary structural elements. Magnetic interactions between probes localized at positions 163, 217 and 226 in singly and doubly labeled apoA-I gave inter- and intramolecular distance information, providing a basis for mapping apoA-I tertiary and quaternary structure. Spectra of apoA-I in reconstituted HDL revealed a lipid-induced transition of defined random coils and beta-strands into alpha-helices. This conformational switch is analogous to triggered events in viral fusion proteins and may serve as a means to overcome the energy barriers of lipid sequestration, a critical step in cholesterol efflux and HDL assembly.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609-1673, USA. moda@chori.org
authors.forename: Michael N
authors.initials: MN
authors.lastname: Oda
authors.forename: Trudy M
authors.initials: TM
authors.lastname: Forte
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
authors.forename: John C
authors.initials: JC
authors.lastname: Voss
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009589:Nitrogen Oxides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013113:Spin Labels
chemical_list: D016632:Apolipoprotein A-I; D008055:Lipids; D008075:Lipoproteins, HDL; D009589:Nitrogen Oxides; D013113:Spin Labels; C039900:nitroxyl