Identification of residues in alpha-macroglobulins important for binding to the alpha2-macroglobulin receptor/Low density lipoprotein receptor-related protein.
Variants of the receptor binding domain of both human alpha2-macroglobulin and the corresponding domain of hen egg white ovomacroglobulin have been expressed in Escherichia coli and refolded in vitro. Competition experiments with methylamine-treated alpha2-macroglobulin for binding to the multifunctional alpha2-macroglobulin receptor identify two Lys residues (residues 1370 and 1374 in human alpha2-macroglobulin) spaced by three amino acid residues as crucial for receptor binding. From this result and mutational evidence from other ligands for the alpha2-macroglobulin receptor, a tentative sequence motif for receptor binding is proposed.
Nielsen
K L
KL
Department of Chemistry, University of Aarhus, 8000 Arhus C, Denmark.
Holtet
T L
TL
Etzerodt
M
M
Moestrup
S K
SK
Gliemann
J
J
Sottrup-Jensen
L
L
Thogersen
H C
HC
D000595:Amino Acid Sequence; D000818:Animals; D015387:Egg Proteins, Dietary / Q000378:metabolism; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000511:alpha-Macroglobulins / Q000235:genetics / Q000378:metabolism*
D015387:Egg Proteins, Dietary; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins