title: Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes.
abstract: Spherical high density lipoproteins (HDL) predominate in human plasma. However, little information exists on the structure of the most common HDL protein, apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We produced spherical HDL by incubating reconstituted discoidal HDL with physiological plasma-remodeling enzymes and compared apoA-I structure in discs and spheres of comparable diameter (79-80 and 93-96 A). Using cross-linking chemistry and mass spectrometry, we determined that the general structural organization of apoA-I was overall similar between discs and spheres, regardless of diameter. This was the case despite the fact that the 93 A spheres contained three molecules of apoA-I per particle compared with only two in the discs. Thus, apoA-I adopts a consistent general structural framework in HDL particles-irrespective of shape, size and the number of apoA-Is present. Furthermore, a similar cross-linking pattern was demonstrated in HDL particles isolated from human serum. We propose the first experiment-based molecular model of apoA-I in spherical HDL particles. This model provides a new foundation for understanding how apoA-I structure modulates HDL function and metabolism.
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
authors: R A Gangani D
authors: RA
authors: Silva
authors: Rong
authors: R
authors: Huang
authors: Jamie
authors: J
authors: Morris
authors: Jianwen
authors: J
authors: Fang
authors: Elena O
authors: EO
authors: Gracheva
authors: Gang
authors: G
authors: Ren
authors: Anatol
authors: A
authors: Kontush
authors: W Gray
authors: WG
authors: Jerome
authors: Kerry-Anne
authors: KA
authors: Rye
authors: W Sean
authors: WS
authors: Davidson
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D013058:Mass Spectrometry; D010316:Particle Size; D011487:Protein Conformation
chemical_list: D016632:Apolipoprotein A-I; D003432:Cross-Linking Reagents; D004798:Enzymes; D008075:Lipoproteins, HDL