The structural basis for amyloid formation by plasma apolipoproteins: a review

Abstract

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 α-helices and limited conformational stability in the absence of lipid. Other proteins that form amyloid such as α-synuclein and serum amyloid A also contain amphipathic α-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 α-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.