Structural models of human apolipoprotein A-I: a critical analysis and review

Human apolipoprotein (apo) A-I has been the subject of intense investigatio n because of its well-documented antiatherogenic properties. About 70% of t he protein found in high density lipoprotein complexes is apo A-I, a molecu le that contains a series of highly homologous amphiphatic alpha -helices. A number of significant experimental observations have allowed increasing s ophisticated structural models for both the lipid-bound and the lipid-free forms of the apo A-I molecule to be tested critically. It seems clear, for example, that interactions between amphipathic domains in apo A-I may be cr ucial to understanding the dynamic nature of the molecule and the pathways by which the lipid-free molecule binds to lipid, both in a discoidal and a spherical particle. The state of the art of these structural studies is dis cussed and placed in context with current models and concepts of the physio logical role of apo A-I and high-density lipoprotein in atherosclerosis and lipid metabolism. (C) 2001 Elsevier Science B.V. All rights reserved.