Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes.
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.
Silva
R A Gangani D
RA
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
Huang
Rong
R
Morris
Jamie
J
Fang
Jianwen
J
Gracheva
Elena O
EO
Ren
Gang
G
Kontush
Anatol
A
Jerome
W Gray
WG
Rye
Kerry-Anne
KA
Davidson
W Sean
WS
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
D016632:Apolipoprotein A-I; D003432:Cross-Linking Reagents; D004798:Enzymes; D008075:Lipoproteins, HDL