title: Predicting the structure of apolipoprotein A-I in reconstituted high-density lipoprotein disks.
abstract: In reconstituted high-density lipoproteins, apolipoprotein A-I and phosphatidylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-1 bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high-density lipoprotein disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoylphosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8-A shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of a reconstituted high-density lipoprotein were simulated. In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails.
authors.affiliation: Theoretical Biophysics, Beckman Institute and Department of Physics, College of Medicine at Urbana-Champaign, University of Illinois, Urbana 61801, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Phillips
authors.forename: W
authors.initials: W
authors.lastname: Wriggers
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Jonas
authors.forename: K
authors.initials: K
authors.lastname: Schulten
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014867:Water / Q000737:chemistry
chemical_list: D016632:Apolipoprotein A-I; D008051:Lipid Bilayers; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D014867:Water; C028694:1-palmitoyl-2-oleoylphosphatidylcholine