Structure and Function of Apolipoprotein E
Our research focuses on the structural and functional relationships of apolipoprotein (apo) E in lipoprotein metabolism, heart disease, and neurodegenerative diseases, including Alzheimer’s disease. ApoE is a 299–amino acid, single-chain protein with two structural domains that also define functional domains (Figure 1).web.jpg)
The three common human isoforms, apoE2, apoE3, and apoE4, differ at two positions in the molecule and have very different metabolic properties and impacts on disease. ApoE3 (Cys-112, Arg-158) binds normally to low density lipoprotein (LDL) receptors and is associated with normal lipid metabolism, whereas apoE2 (Cys-112, Cys-158) binds defectively to LDL receptors and, under certain circumstances, is associated with the genetic disorder type III hyperlipoproteinemia. ApoE4 (Arg-112, Arg-158) binds normally to LDL receptors but is associated with elevated cholesterol levels and increased risk for cardiovascular disease. In addition, apoE4 is a major risk factor for Alzheimer’s disease and for poor outcome from head injury and stroke. Our objective is to determine how the structural and biophysical properties of apoE influence its metabolic properties and contribute to its isoform-specific effects in disease and injury.
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