Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor.
We describe a cell surface protein that is abundant in liver and has close structural and biochemical similarities to the low density lipoprotein (LDL) receptor. The complete sequence of the protein containing 4544 amino acids is presented. From the sequence a remarkable resemblance to the LDL-receptor and epidermal growth factor (EGF) precursor is apparent. Three types of repeating sequence motifs entirely account for the extracellular domain of the molecule. These are arranged in a manner resembling four copies of the ligand binding and the EGF-precursor homologous region of the LDL-receptor. Following a proline-rich segment of 17 amino acids are found six consecutive repeats with close homology to EGF. A single membrane-spanning segment precedes a carboxy-terminal 'tail' of 100 amino acids. This contains two seven-amino acid sequences with striking homology to the cytoplasmic tail of the LDL-receptor in the region that contains the signal for clustering into coated pits. The mRNA for this protein is most abundant in liver, brain and lung. By using an antibody raised against a 13-amino acid peptide corresponding to the deduced amino acid sequence of the carboxy-terminus of the protein we have demonstrated its existence on the cell surface and its abundance in liver. Like the LDL-receptor this protein also strongly binds calcium, a cation absolutely required for binding of apolipoproteins B and E to their receptors. We propose that this LDL-receptor related protein (LRP) is a recycling lipoprotein receptor with possible growth-modulating effects.
Herz
J
J
European Molecular Biology Laboratory, Heidelberg, FRG.
Hamann
U
U
Rogne
S
S
Myklebost
O
O
Gausepohl
H
H
Stanley
K K
KK
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011498:Protein Precursors; D011971:Receptors, Immunologic; D011973:Receptors, LDL; C042652:epidermal growth factor precursor; D004815:Epidermal Growth Factor; D002118:Calcium