Structural relationship of an apolipoprotein (a) phenotype (570 kDa) to plasminogen: homologous kringle domains are linked by carbohydrate-rich regions.
At least six allelic forms of apolipoprotein(a), differing in molecular mass, could be detected by immunoblot analysis. One of these phenotypes with a molecular mass of 570 kDa has been investigated. After reduction and carboxymethylation it was digested with trypsin and the resulting peptides were separated by gel filtration and reverse phase HPLC. The tryptic fragments sequenced comprised a total of 356 amino acids. The N-terminus of apo(a) was highly homologous to the start of the kringle 4 domain from human plasminogen and the majority of the tryptic peptides isolated was also homologous to sequences from this kringle. At least five homologous "kringle 4" domains are present in apolipoprotein(a) whereby one domain occurs more frequently than the others. A carbohydrate-rich peptide was also obtained in high yield. This glycopeptide connects two "kringle 4" domains and contains one N-glycoside within the kringle and six potential O-glycosides in the linking region. From the recovery it can be estimated that this peptide occurs several times within the whole apolipoprotein (a) sequence. The high carbohydrate content is in sharp contrast to that of human plasminogen. Other peptides sequenced indicate that apo (a) also contains domains homologous to the kringle 5 and protease regions of plasminogen. No unique peptides were found. These studies suggest that apolipoprotein (a) could have arisen through duplication of specific regions from the human plasminogen gene. The size heterogeneity of apo (a) might then be explained by differences in the numbers of gene duplications.
Abteilung Immunchemie, Max-Planck-Institut für experimentelle Medizin, Göttingen.
H
H
Kratzin
V W
VW
Armstrong
M
M
Niehaus
N
N
Hilschmann
D
D
Seidel
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001054:Apolipoproteins A / Q000032:analysis* / Q000235:genetics; D002241:Carbohydrates / Q000032:analysis*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D010641:Phenotype; D010958:Plasminogen / Q000032:analysis* / Q000235:genetics; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate
D000596:Amino Acids; D001054:Apolipoproteins A; D002241:Carbohydrates; D010446:Peptide Fragments; D012967:Sodium Dodecyl Sulfate; D010958:Plasminogen