The apolipoprotein multigene family: Structure, expression, evolution, and molecular genetics

Abstract

The plasma apolipoproteins can be classified into two subgroups: the soluble apolipoproteins including apolipoprotein (apo) A-I, A-II, A-IV, C-I, C-II, C-III, and E, and the apoBs including apoB-100 and apoB-48. The soluble apolipoproteins have very similar genomic structures, each having a total of three introns at the same locations; apoA-IV is an exception in that it has lost its first intron. Using the exon/intron junctions as reference points, we can obtain an alignment of the coding regions of all the soluble apolipoprotein genes. The mature peptide regions of the genes are almost completely made up of tandem repeats of 11 codons. The part of mature peptide region encoded by exon 3 contains a common block of 33 codons, whereas the part encoded by exon 4 contains a much more variable number of internal repeats of 11 codons. On the basis of the degree of homology of the various sequences, and the pattern of the internal repeats in these genes, an evolutionary tree has been proposed for the soluble apolipoprotein genes. ApoB-100 differs considerably from the soluble apolipoproteins. It is the largest apolipoprotein containing 4536 amino acid residues. Two types of internal repeats are identified in apoB-100: amphipathic alpha-helical repeats and proline-containing repeats with high beta-sheet content. The apoB gene contains 29 exons and 28 introns. Its evolutionary relationship to the soluble apolipoprotein genes is unclear. The 3' end of the apoB gene contains a region of variable number of tandem 12-16-base pair repeats.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices

“…Eight repeats contain 22 amino acids, while repeats 3 and 9 are composed of 11 amino acids. Seven of the ten repeats are separated by the helix-breaking amino acid proline [61]. These ‘breaks’ have been suggested to impart flexibility to the protein allowing it to ‘bend’ around the periphery of HDL particles [62,63].…”

The use of chemical cross-linking and mass spectrometry to elucidate the tertiary conformation of lipid-bound apolipoprotein A-I

“…Eight of these repeats contain 22 amino acids while two contain 11 amino acids, most of which are separated by helix-breaking amino acids such as proline [8]. A number of investigators have noted that the frequency of these 'breaks' may impart flexibility to apoA-I allowing it to bend around the periphery of the spherical HDL particle [9,10].…”

Three-dimensional models of HDL apoA-I: implications for its assembly and function

“…Eight of these repeats contain 22 amino acids, whereas two contain 11 amino acids. Helix-breaking amino acids such as proline (27) separate seven out of the ten repeats. Several investigators have suggested that the frequency of these "breaks" may impart flexibility to apoA-I, allowing it to bend around the periphery of the spherical HDL particle (28,29).…”