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Lipid-bound structure of an apolipoprotein E-derived peptide
Vincent Raussens1, Carolyn M Slupsky, Brian D Sykes
1Protein Engineering Network Centres of Excellence and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
The Journal of Biological Chemistry
|April 24, 2003
Summary
Apolipoprotein E (apoE) undergoes structural changes upon lipid binding, forming a helical structure that interacts with LDL receptors. This study reveals dynamic features of lipid-bound apoE, clarifying its receptor binding mechanism.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biophysics
Background:
- Apolipoprotein E (apoE) is crucial for lipid homeostasis and interacts with the low-density lipoprotein (LDL) receptor family.
- Lipid binding induces conformational changes in apoE, enabling receptor recognition.
Purpose of the Study:
- To investigate the structural and dynamic changes in apoE upon lipid binding.
- To elucidate the molecular basis of apoE-LDL receptor interactions.
Main Methods:
- Multidimensional heteronuclear NMR spectroscopy was used to determine the structure of apoE peptide (126-183) bound to dodecylphosphocholine (DPC) micelles.
- NMR relaxation studies and spectral density analysis were performed to assess peptide dynamics.
Main Results:
- The apoE peptide (126-183) formed a continuous amphipathic helix when bound to DPC micelles.
- NMR relaxation data indicated the helical peptide was constrained by the micelle, exhibiting isotropic tumbling.
- Residues 150-183 showed greater motional freedom than residues 134-149, suggesting localized dynamics within the bound peptide.
Conclusions:
- Lipid binding induces a helical conformation in apoE, facilitating interaction with LDL receptors.
- The study provides insights into the dynamic nature of lipid-bound apoE and its implications for receptor binding.