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Sub-micellar phospholipid accelerates amyloid formation by apolipoprotein C-II
D M Hatters1, L J Lawrence, G J Howlett
1Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Vic. 3010, Australia.
FEBS Letters
|April 20, 2001
Summary
Lipid-free apolipoprotein C-II (apoC-II) forms amyloid fibrils. Short-chain phospholipids like DHPC can inhibit or accelerate apoC-II amyloid formation depending on concentration, impacting in vivo folding pathways.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Lipid-free human apolipoprotein C-II (apoC-II) adopts an amyloidogenic beta-sheet conformation.
- Lipid-bound apoC-II typically exists in an alpha-helical structure.
- Amyloid formation is implicated in various diseases.
Purpose of the Study:
- To investigate the influence of the short-chain phospholipid dihexanoylphosphatidylcholine (DHPC) on apoC-II amyloid formation.
- To determine how DHPC concentration affects apoC-II's secondary structure and aggregation propensity.
Main Methods:
- Spectroscopic analysis (e.g., circular dichroism) to assess protein secondary structure.
- Amyloid formation assays to quantify fibril aggregation.
- Varying concentrations of DHPC to study dose-dependent effects.
Main Results:
- Micellar concentrations of DHPC (16 mM) increased apoC-II's alpha-helical content and inhibited amyloid formation.
- Sub-micellar concentrations of DHPC (below 8 mM) significantly accelerated apoC-II amyloid formation by 6-fold.
- ApoC-II's folding pathway and aggregation are sensitive to phospholipid environment.
Conclusions:
- Individual phospholipid molecules can modulate apoC-II's structural conformation and amyloidogenic potential.
- The concentration-dependent effects of phospholipids like DHPC are critical in determining apoC-II's in vivo folding behavior.
- These findings highlight the role of lipid-protein interactions in regulating protein aggregation pathways.
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