Structural similarities in the repeat sequences of plasma apolipoproteins, A-I, A-IV, and E.

Abstract

The presence of 22-residue repeats, each with a preferential potential to form an amphipathic alpha-helix, is a unique feature of the plasma apolipoproteins. There are 27 such repeats in the three human apolipoproteins A-I, A-IV, and E. The extent of similarities and differences among these repeats have been estimated by computing correlation coefficients, Dayhoff scores, secondary structure difference profiles, and discrete Fourier transforms. The results reveal that there is a high level of similarity among the repeats of apo A-IV, and a low level of similarity in the repeats of apo E. Within each protein, similarity among some specified repeat pairs is distinctively higher than the others. A high order of similarity is also found among certain segments of each protein with those in the other two. The repeats prefer a mostly alpha-helical structure that is amphipathic in nature. Among the repeats of the three proteins, those of apo E show a high level of divergence among themselves. A consensus alignment of the residues of the 27 repeats into a hydrophobic versus hydrophilic pattern brings to focus the possible specific structure-stabilizing factors, such as the leucine zipper and the salt bridge. The recently reported crystal structures of the human apolipoprotein E and locust apolipophorin-III support many of the predictions made in this study.