Apolipoprotein B-100: conservation of lipid-associating amphipathic secondary structural motifs in nine species of vertebrates

Abstract

Development of a computer program called LOCATE allowed us to show that human apolipoprotein B-100 is composed of five domains, NH2-α1-β1-α2-β2-α3-COOH, enriched, alternately, in amphipathic α helixes and amphipathic β strands. Using updated versions of this program, here we compare the complete sequence of human apolipoprotein B-100 with partial sequences from eight additional species of vertebrates (chicken, frog, hamster, monkey, mouse, pig, rat, and rabbit). The lipid-associating amphipathic α helixes cluster in domains α2 (between residues 2075 ± 25 and 2575 ± 25) and α3 (between residues 4100 ± 100 and 4550 ± 50) in all species for which those regions have been sequenced but with little conservation of individual helixes. Lipid-associating amphipathic β strands cluster in domains β1 (approximately residues 827-2000) and β2 (approximately residue 2571 to residue 4000 ± 50) in all species for which these regions have been sequenced, with conservation of several individual amphipathic β strands. Hydrophobic segments are present in apolipoprotein B-100 sequences of all nine species but the frequency of occurrence is no greater than generally found in β sheet-containing proteins. We conclude that four alternating lipid-associating domains, -β1-α2-β2-α3-COOH, are common supramolecular features of apolipoprotein B-100 in nine vertebrate species.—Segrest, J. P., M. K. Jones, V. K. Mishra, V. Pierotti, S. H. Young, J. Borén, T. L. Innerarity, and N. Dashti. Apolipoprotein B-100: conservation of lipid-associating amphipathic secondary structural motifs in nine species of vertebrates. J. Lipid Res. 1998. 39: 85–102.

Keywords

• amphipc α helixes
• amphipathic β strands
• hydrophobic amino acid sequences
• plasma lipoproteins
• computer analysis of amphipathic motifs
• low density lipoprotein