Apolipoprotein primary sequence

Given the widespread occurrence of sequences in apolipoproteins that evidently code for amphipathic helices, it is not surprising that many workers have attempted to identify possible secondary structural elements in apolipoproteins and to predict possible tertiary interactions and overall arrangements of secondary structure elements when these proteins are bound to lipids (Edelstein et al., 1979). Here we discuss models for apoA-1 and apoE-3 developed by Nolte and Atkinson (1992). These models resulted from an examination of the primary sequence of human plasma and apoA-1 and apoE-3 using a variety of approaches, and an integration of the resulting data into unihed predictions for the secondary structures of those molecules. 

The key structural features predicted for the amphipathic helix by the original model (Segrest et al., 1974) enabled three laboratories to study independently how amino acid variability determined the properties of the amphipathic helix (Kanellis et al., 1980 Fukushima et al., 1980 Sparrow et al., 1981). The strategy adapted by these investigators was based, not on the primary sequence of naturally occurring apolipoproteins, but on incorporating the periodicity of the secondary structural features of the amphipathic helix motif into the sequences of the peptide analogs. 

Apolipoprotein A-I is the primary protein component of HDL.23 2513 Most of the 243 residues consist of a nearly continuous amphipathic a helix with kinks at regularly spaced proline residues.26 28 Two disulfide-linked ApoA-I molecules may form a belt that encircles the discoid lipoprotein.2513 ApoA-II is the second major HDL protein, but no dearly specialized function has been identified.29 30 ApoA-I, II, and IV, apoC-I, II, and III, and apoE all have multiple repeats of 22 amino acids with sequences that suggest amphipathic helices. Tire 391-residue ApoA-IV has 13 tandem 22-residue repeats. Proline and glycine are present in intervening hinge regions.23 This may enable these proteins to spread over and penetrate the surfaces of the lipoprotein micelles. Most of these proteins are encoded by a related multigene family.7 303... 

The primary amino acid sequence of apoA-I has been published by Brewer and colleagues (B43) and, with a few minor differences, by Baker et al. (Bl). As with other apolipoproteins that have been sequenced, there are no long sequences of hydrophobic or hydrophilic amino acids, but there is evidence that amphipathic regions of a-helices are formed during combination with lipid, with one face of each helical region more hydrophobic than its opposite face (07). 

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