A novel member of the LDL receptor gene family with eleven binding repeats is structurally related to neural adhesion molecules and a yeast vacuolar protein sorting receptor.
We now have discovered and characterized a novel multi-domain protein and classified it as a member of the LDL receptor gene family. The approximately 250 kDa membrane protein, termed LR11, highly conserved in man, rabbit and chicken, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. The features of this highly conserved and complex mosaic protein suggest the importance of the ever expanding LDL receptor gene family in the evolution and proposed multifunctionality.
Yamazaki
H
H
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Bujo
H
H
Saito
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D004705:Endocytosis; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D005656:Fungal Proteins; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D011973:Receptors, LDL; C102582:SORL1 protein, human