Cloning and sequencing of bovine apolipoprotein E complementary DNA and molecular evolution of apolipoproteins E, C-I, and C-II.
Apolipoprotein (apo) E, a major protein component of plasma lipoproteins, is a physiological ligand for the low density lipoprotein (LDL) receptor as well as for a specific apoE receptor; it is therefore an important modulator of lipoprotein metabolism. In this study we cloned and sequenced bovine apoE complementary DNA. Comparison of nucleotide substitution rates shows that apoE is less conservative than apoA-I and evolves about 30% faster than an average mammalian protein. Although apoE is not a conservative protein, several regions have been well conserved among all eight mammalian sequences now available. These include a 33-amino-acid block immediately upsteam from the third intron/exon junction and the LDL receptor binding region. We have also compared published apoC-I and apoC-II sequences. Both proteins are less conservative than apoE. In particular, apoC-I shows no well-conserved region except for a small region in the common 33-amino-acid block, suggesting that the function of apoC-I does not have stringent structural requirements. On the other hand, in apoC-II the region encoded by exon 4, which consists of the last 29 amino acids of the polypeptide, has been rather well conserved, probably because this region is important for the activation of lipoprotein lipase and chylomicron and very low density lipoprotein metabolism.
Yang
Y W
YW
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Chan
L
L
Li
W H
WH
D000595:Amino Acid Sequence; D000818:Animals; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D001056:Apolipoproteins C / Q000097:blood / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry*; D004285:Dogs; D006168:Guinea Pigs; D006801:Humans; D008251:Macaca; D051379:Mice; D008969:Molecular Sequence Data; D010215:Papio; D011817:Rabbits; D051381:Rats
D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D004247:DNA