Submitted on December 27, 2005
Revised on March 27, 2006
Accepted on April 21, 2006
C-termini interactions of apolipoprotein E4 respond to the postprandial state
Sarada D. Tetali, Madhu S. Budamagunta, John C. Voss, and John C. Rutledge
Internal Medicine, University of California, Davis, Davis, CA 95616
Corresponding Author: skanakagiri{at}ucdavis.edu
Elevation of triglyceride-rich lipoproteins (TGRL) in the postprandial state is associated with atherosclerosis. We investigated whether the postprandial state induced structural changes at the apoE4 C-terminus, its principal lipid binding domain, using electron paramagnetic resonance spectroscopy (EPR) of a site-directed spin-label attached to the cysteine of apoE4-W264C. Spin coupling between labels located in the C-termini was followed after mixing with pre- and post-prandial human plasma samples. Our results indicate that postprandial plasma triggers a reorganization of the protein such that the dipolar broadening is diminished indicating a reduction in C-terminal interaction. Loss in spectral broadening was directly correlated with an increase in postprandial plasma triglycerides and was reduced with delipidated plasma. The spin-labeled apoE4 displayed a lipid preference of VLDL>LDL>HDL in the pre- and post-prandial states. ApoE4 shift to VLDL during postprandial state was accompanied by a loss in spectral broadening of the protein. These findings suggest that apoE4 associated with LDL maintains self-association via its C-terminus and such association is diminished in VLDL-associated protein. Lipolyzed TGRL reflected a depletion of C-terminal interaction of apoE4. Addition of palmitate to VLDL gave similar response as lipolyzed TGRL, suggesting lipolysis products play a major role in reorganizing apoE4 during postprandial state.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
