Sub-micellar phospholipid accelerates amyloid formation by apolipoprotein C-II.
Lipid-free human apolipoprotein C-II (apoC-II) forms amyloid fibrils with characteristic beta-structure. This conformation is distinct from the alpha-helical fold of lipid-bound apoC-II. We have investigated the effect of the short-chain phospholipid, dihexanoylphosphatidylcholine (DHPC) on amyloid formation by apoC-II. The alpha-helical content of apoC-II increases in the presence of micellar DHPC (16 mM) and amyloid formation is inhibited. However, at sub-micellar DHPC concentrations (below 8 mM) amyloid formation is accelerated 6 fold. These results suggest that individual phospholipid molecules in vivo may exert significant effects on amyloid folding pathways.
Hatters
D M
DM
Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Vic. 3010, Australia.
Lawrence
L J
LJ
Howlett
G J
GJ
D000686:Amyloidosis / Q000378:metabolism*; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008823:Micelles; D008954:Models, Biological; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D010713:Phosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017510:Protein Folding; D020836:Protein Structure, Quaternary / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D013997:Time Factors
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D008823:Micelles; D010713:Phosphatidylcholines; C032166:1,2-hexanoylphosphatidylcholine