Comparative models for human apolipoprotein A-I bound to lipid in discoidal high-density lipoprotein particles.
We have constructed a series of models for apolipoprotein A-I (apo A-I) bound to discoidal high-density lipoprotein (HDL) particles, based upon the molecular belt model [Segrest, J. P., et al. (1999) J. Biol. Chem. 274, 31755-31758] and helical hairpin models [Rogers, D. P., et al. (1998) Biochemistry 37, 11714-11725], and compared these with picket fence models [Phillips, J. C., et al. (1997) Biophys. J. 73, 2337-2346]. Molecular belt models for discoidal HDL particles with differing diameters are presented, illustrating that the belt model can explain the discrete changes in HDL particle size observed experimentally. Hairpin models are discussed for the binding of apo A-I to discoidal HDL particles with diameters identical to those for the molecular belt model. Two models are presented for the binding of three monomers of apo A-I to a 150 A diameter discoidal HDL particle. In one model, two monomers of apo A-I bind to the exterior of the HDL particle in an antiparallel belt, with a third monomer of apo A-I bound to the disk in a hairpin conformation. In the second model, all three monomers of apo A-I are bound to the discoidal HDL particle in a hairpin conformation. Previously published experimental data for each model are reviewed, with FRET favoring either the belt or hairpin models over the picket fence models for HDL particles with diameters of 105 A. Naturally occurring mutations appear to favor the belt model for the 105 A particles, while the 150 A HDL particles favor the presence of at least one hairpin.
Department of Biochemistry and Molecular Genetics and Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Anthony E
AE
Klon
Jere P
JP
Segrest
Stephen C
SC
Harvey
D016632:Apolipoprotein A-I / Q000737:chemistry*; D003198:Computer Simulation; D004735:Energy Transfer; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry*; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
D016632:Apolipoprotein A-I; D008074:Lipoproteins; D008075:Lipoproteins, HDL; C034366:discoidal lipoproteins