The structural basis for amyloid formation by plasma apolipoproteins: a review.
The formation of amyloid and other protein deposits in vivo is synonymous with many pathological conditions such as Alzheimer's disease, Creutzfeldt-Jakob disease and Parkinson's disease. Interestingly, many plasma apolipoproteins are also associated with amyloid deposits, including apolipoprotein (apo) A-I, apoA-II and apoE. Apolipoproteins share a number of structural and conformational properties, namely a large proportion of class A amphipathic alpha-helices and limited conformational stability in the absence of lipid. Other proteins that form amyloid such as alpha-synuclein and serum amyloid A also contain amphipathic alpha-helical domains similar to those found in apolipoproteins. In this review we develop a hypothesis to account for the widespread occurrence of apolipoproteins in amyloid deposits. We describe the conformational stability of human apoC-II and the stabilization of alpha-helical structure in the presence of phospholipid. We propose that lipid-free apoC-II forms partially folded intermediates prone to amyloid formation. Parameters that affect apolipoprotein lipid binding in vivo, such as protein and lipid oxidation or protein truncations and mutations, could promote apolipoprotein-related pathologies including those associated within amyloid deposits of atherosclerotic plaques.
Hatters
Danny M
DM
Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia. dannymh@unimelb.edu.au
Howlett
Geoffrey J
GJ
D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D001056:Apolipoproteins C / Q000737:chemistry; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D004355:Drug Stability; D006801:Humans; D015394:Molecular Structure; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000682:Amyloid; D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001056:Apolipoproteins C