title: Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif.
abstract: The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers' disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly "nanodisc" structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.
authors.affiliation: Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK. I.W.Hamley@reading.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Castelletto
authors.forename: I W
authors.initials: IW
authors.lastname: Hamley
authors.forename: M
authors.initials: M
authors.lastname: Reza
authors.forename: J
authors.initials: J
authors.lastname: Ruokolainen
mesh_terms: D020816:Amino Acid Motifs; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000648:ultrastructure; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000648:ultrastructure; D055666:Lipopeptides / Q000737:chemistry* / Q000648:ultrastructure; D008422:Materials Testing; D008563:Membrane Lipids / Q000737:chemistry*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping
chemical_list: D016632:Apolipoprotein A-I; D015815:Cell Adhesion Molecules; D055666:Lipopeptides; D008563:Membrane Lipids; D046912:Multiprotein Complexes; D009842:Oligopeptides; C046617:arginyl-glycyl-aspartyl-serine