Human apolipoprotein B: analysis of internal repeats and homology with other apolipoproteins

Apolipoprotein B (apoB) is the major protein component of plasma low density lipoproteins (LDL) and, through its binding to the LDL receptor, it plays a prominent role in lipoprotein metabolism and in the development of atherosclerosis. Specially developed computer programs were applied to detect potential internal repeats in the human apoB sequence and homology of some of these repeats with other apolipoproteins. The simultaneous computer alignment of several (repeated) sequences, carried out in an iterative way to generate consensus sequences, showed the presence of repeated amphipathic helical regions and of repeated hydrophobic proline-rich domains. Extensive Monte-Carlo statistics were used to demonstrate the statistical significance of the internal repeats. Both classes of repeats may contribute to the specific lipid-binding characteristics of apoB. Additional homology, detected between apoB and apoE, the other apolipoprotein-ligand of the LDL receptor, further defined the structural requirements for this receptor-ligand interaction. The computer programs developed in this study should also be useful for detecting internal repeats in other proteins.