Structural and functional properties of apolipoprotein A-I mutants.

Abstract

Apolipoprotein (apo) A-I is composed of 243 amino acid residues that fold into amphipathic helixes, and plays a central role in the high density lipoprotein (HDL) metabolism. Familial apoA-I deficiency is a rare metabolic disorder of which three cases have been characterized at a molecular level in western Japan. However, in subjects with apoA-I deficiency, coronary artery disease was not always present. One apo A-I deficiency was compound heterozygous apoA-I mutant for a TATA box mutation and a structural nonsense mutation. To date, screening analysis in our laboratory has identified nine genetically-determined structural mutations of apo A-I. We have also characterized these apo A-I mutations, including apoA-I (Glu235del) Nichinan. Few structural mutations were associated with altered HDL cholesterol levels.