Apolipoprotein E: Structure-Function Relationships

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This chapter focuses on the role of apoE in lipoprotein metabolism and the most completely described function of the protein. Apolipoprotein E (apoE) is one of the best characterized in terms of its structural and functional properties. Plasma apolipoproteins regulate lipoprotein metabolism and control the transport and redistribution of lipids among tissues and cells. Apolipoproteins can perform one of three major roles because of their ability to bind lipid. First, apolipoproteins stabilize the pseudomicellar structure of lipoprotein particles. Second, apolipoproteins can act as cofactors or activators of various enzymes or lipid transfer proteins that participate in the metabolism of “remodeling” of lipoproteins as they circulate in plasma. A third function of plasma apolipoproteins-one that is restricted to apoB100 and ApoE- is to serve as a ligand for cell surface lipoprotein receptors. The three-dimensional structure of a 22-kDa fragment of human apoE is solved by X-ray crystallography; the relation of this structure to the role of apoE in lipoprotein metabolism is discussed, together with a critical and extensive examination of the chemistry and biology of this apolipoprotein, which plays such a central role in lipoprotein metabolism. Apolipoprotein E has three major isoform in the human population, which affect lipoprotein metabolism differently, resulting in different levels of the plasma lipoproteins. The role of apoE as a cofactor in lipolytic processing of triglyceride-rich lipoproteins, and the role of apoE in the reverse cholesterol transport process are described.

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