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C-terminal interactions of apolipoprotein E4 respond to the postprandial state
Sarada D Tetali1, Madhu S Budamagunta, John C Voss
1Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, University of California, Davis, 95616, USA. skanakagiri@ucdavis.edu
Journal of Lipid Research
|April 25, 2006
Summary
Postprandial plasma triglycerides reorganize apolipoprotein E4 (apoE4) structure, reducing C-terminal interactions. This structural change, linked to atherosclerosis risk, is associated with apoE4
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Science
Background:
- Elevated triglyceride-rich lipoproteins (TGRLs) post-meal are linked to atherosclerosis.
- Apolipoprotein E4 (apoE4) plays a role in lipoprotein metabolism and cardiovascular disease.
Purpose of the Study:
- To investigate structural changes in the apoE4 C-terminus during the postprandial state.
- To understand how postprandial lipemia affects apoE4's interaction with lipoproteins.
Main Methods:
- Site-directed spin labeling of apoE4 at Cys (apoE4-W264C).
- Electron paramagnetic resonance (EPR) spectroscopy to monitor spin coupling and protein conformation.
- Incubation of labeled apoE4 with preprandial and postprandial human plasma.
Main Results:
- Postprandial plasma induced a reduction in apoE4 C-terminal interactions, indicated by diminished EPR spectral broadening.
- This reduction correlated with increased postprandial plasma triglycerides and was less pronounced with delipidated plasma.
- ApoE4 preferentially bound VLDL > LDL > HDL, with a shift towards VLDL in the postprandial state, accompanied by reduced spectral broadening.
Conclusions:
- Postprandial lipemia reorganizes apoE4 structure, diminishing C-terminal self-association.
- This reorganization is particularly evident when apoE4 is associated with VLDL, suggesting lipolysis products influence apoE4 conformation.
- Understanding these structural changes may offer insights into apoE4's role in atherosclerosis development.