Rat apolipoprotein A-IV contains 13 tandem repetitions of a 22-amino acid segment with amphipathic helical potential.

Abstract

Apolipoprotein (apo) A-IV is a 46,000 MW protein that is a major component of rat high density lipoproteins and chylomicrons. From a rat intestinal c[complementary]DNA library, a full-length apo A-IV clone of 1423 base pairs was isolated and its nucleotide sequence determined. The 1173-nucleotide coding region specifies a protein of 391 amino acids, which includes a 20-amino acid signal peptide. The portion of the cDNA sequence representing the mature plasma protein contains a 66-nucleotide subsequence that is repeated at least 13 times. Although each repeated unit shows some sequence variation, base changes in comparably positioned codons generally conserve the chemical type, if not the identity, of the corresponding amino acids. Nine of the 13 22-amino acid repeat units in the derived protein sequence begin with Pro and most of these docosapeptides are predicted to have a high content of .alpha.-helix according to Chou-Fasman rules. When hydration potentials of individual residues are considered, many of the helices are shown to be amphipathic and may thus constitute lipid-binding domains with the ability to activate lecithin:cholesterol acyltransferase. The structure and organization of the repeat units of rat apo A-IV bear a striking similarity to a corresponding repeated sequence block in human apo A-I. This finding raises the possibility of close tandem linkage of the apo A-I and A-IV genes and suggests unequal crossing-over as a mechanism for the evolution of these genes.