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Apolipoprotein A-I conformation in discoidal particles: evidence for alternate structures
L Calabresi1, Q H Meng, G R Castro
1Lipoproteins and Atherosclerosis Group, University of Ottawa Heart Institute, Ontario, Canada.
Biochemistry
|June 29, 1993
Summary
Lipid binding dramatically alters apolipoprotein A-I (apoA-I) conformation, exposing some regions and masking others. Particle size also influences apoA-I structure within discoidal lipoproteins (LpA-I).
Area of Science:
- Biochemistry
- Lipid Metabolism
- Protein Conformation
Background:
- Apolipoprotein A-I (apoA-I) is the major protein in high-density lipoproteins (HDL).
- Understanding apoA-I conformation is crucial for elucidating HDL function in reverse cholesterol transport.
Purpose of the Study:
- To define the conformation of apolipoprotein A-I (apoA-I) in discoidal particles.
- To investigate how lipid binding and particle size affect apoA-I structure.
Main Methods:
- Reconstituted discoidal lipoproteins (LpA-I) with varying apoA-I content and sizes were prepared.
- Immunoreactivity of apoA-I epitopes was assessed in lipid-free and lipid-bound forms using antibodies.
- Epitope mapping was performed by analyzing antibody competition.
Main Results:
- Lipid binding induced significant conformational changes in apoA-I, altering epitope exposure.
- Particle size within LpA-I classes (Lp2A-I, Lp3A-I) modulated apoA-I conformation, evidenced by differing ED50 values.
- Analysis of antibody competition revealed size-dependent differences in epitope positioning, particularly in the central apoA-I region.
Conclusions:
- Lipid-bound apoA-I adopts a conformation distinct from its lipid-free state.
- Discoidal lipoprotein particle size influences the three-dimensional structure of apoA-I.
- These findings provide insights into the structural plasticity of apoA-I in HDL particles.