Alpha 2-macroglobulin-proteinase complexes, plasminogen activator inhibitor type-1-plasminogen activator complexes, and receptor-associated protein bind to a region of the alpha 2-macroglobulin receptor containing a cluster of eight complement-type repeats.
A region containing sites for ligand binding was localized in the 4525-amino acid residue alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) by ligand- and immunoblotting of proteinase and CNBr digests of the purified human placental protein. 125I-Labeled rat alpha 1-macroglobulin light chain, urokinase-plasminogen activator inhibitor type-1 complex, and alpha 2MR-associated protein all bound to a 75-kDa CNBr-generated fragment (68 kDa after deglycosylation). In addition to the three ligands, the fragment bound a novel monoclonal antibody reacting in the region defined by amino acid residues 1165-1246 as determined by binding to recombinant fragments of alpha 2MR/LRP. The positions of methionine residues in alpha 2MR/LRP suggested that the ligand-binding CNBr fragment contained three disulfide-linked peptides comprising the residues 776-1399. This origin was confirmed by partial amino acid sequencing of the electroblotted fragment and polypeptides generated by reduction of the fragment. The identified region represents 13.6% of the molecular mass (nonglycosylated) of alpha 2MR/LRP and contains one of three large clusters of complement-type repeats.
Moestrup
S K
SK
Institute of Medical Biochemistry, University of Aarhus, Denmark.
Holtet
T L
TL
Etzerodt
M
M
Thøgersen
H C
HC
Nykjaer
A
A
Andreasen
P A
PA
Rasmussen
H H
HH
Sottrup-Jensen
L
L
Gliemann
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003165:Complement System Proteins / Q000737:chemistry; D003488:Cyanogen Bromide; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006023:Glycoproteins; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017395:Plasminogen Activator Inhibitor 1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D003165:Complement System Proteins; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase; D014568:Urokinase-Type Plasminogen Activator; D003488:Cyanogen Bromide