Detailed molecular model of apolipoprotein A-I on the surface of high-density lipoproteins and its functional implications

The major apolipoprotein (apo) A-I containing lipoprotein, high- density li poprotein, is a negative risk factor for cardiovascular disease. An atomic resolution molecular model for lipid-associated apo A-I was recently propos ed in which two apo A-I molecules are wrapped belt-wise around a small disc oidal patch of phospholipid bilayer. Because of its detailed predictions of lipid-associated apo A-I structure, this molecular belt model, if confirme d, provides a blueprint for understanding the molecular mechanisms of rever se cholesterol transport, and thus for the rational design of new classes o f drugs for reversal of atherosclerosis and cardiovascular disease. The det ails and implications of the model are currently being explored by site-dir ected mutagenesis. (Trends Cardiovasc Med 2000;10:246-252). (C) 2001, Elsev ier Science Inc.