Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis

Apolipoprotein (apo) B-100 is a key protein compound of plasma lipid metabo lism. This protein, as a sole component of LDL particles, to a great extent controls the homeostasis of LDL cholesterol in the plasma. Therefore, this protein and its structural variants play an important role in development of hyperlipidemia and atherosclerosis. Intensive research into the structur e and biological functions of apoB-100 has led to identification of its com plete structure as well as the responsible binding sites. With the developm ent of the methods of molecular biology, some structural variants of the ap oB-100 protein that directly affect its binding properties have been descri bed. These are mutations leading to amino acid substitution at positions 35 00 (R3500Q and R3500W) and 3531 (R3531C) that have been shown to decrease t he binding affinity of apoB-100 in vitro. However, only the former mutation s have been unequivocally demonstrated to cause hyperlipidemia in vivo. Thi s minireview is aimed to discuss the impact of apoB-100 and its structural variants on plasma lipid metabolism and development of hyperlipidemia.