Skip to main content
Log in

Chiloscyllium plagiosum low-density lipoprotein receptor: Evolutionary conservation of five different functional domains

  • Articles
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

All five functional domains of the low-density lipoprotein (LDL) receptor were assembled in their modern form more than 450 million years ago, as revealed from the cloning and sequencing of an LDL receptor cDNA fromChiloscyllium plagiosum (banded cat shark). The shark LDL receptor has the same overall architecture as the mammalian and amphibian counterparts. Each of the seven cysteine-rich repeats in the ligand binding domain resembles its counterpart in the human LDL receptor more than it does the other repeats in the shark receptor as suggested by the presence of unique “signature” sequences, indicating that these repeats had already acquired their independent structures by the time of shark development. Furthermore, amino acid sequences of the entire ligand binding domain of shark LDL receptor show 35% identity over a stretch of 294 residues with aLymnaea stagnalis G-protein-linked receptor (LSGLR). The region of homology between these unrelated proteins includes conservation of most of the unique characteristics of the cysteine-rich repeats of LDL receptor at the expected positions in LSGLR. The results presented are consistent with the hypothesis that all seven repeats in the ligand binding domain of LDL receptor may have been lifted directly from an ancestral gene instead of being evolutionary duplications of a single repeat recruited by the primitive LDL receptor from another gene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bell GI, Fong NM, Stempien MM, Wormsted, MA, Caput, D, Ku L, Urdea MS, Rall LB, Sanchez-Pescador R (1986) Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization. Nucleic Acids Res 14:8427–8446

    Google Scholar 

  • Bishop RW (1992) Structure of the hamster low density lipoprotein receptor gene. J Lipid Res 33:549–557

    Google Scholar 

  • Bork P (1991) Shuffled domains in extracellular proteins. FEBS Lett 286:47–54

    Google Scholar 

  • Brown MS, Goldstein JL (1986) A receptor mediated pathway for cholesterol homeostasis. Science 232:34–47

    Google Scholar 

  • Doolittle RF (1984) Evolution of the vertebrate plasma proteins. In: Putnam FW (ed) The plasma proteins: structure, function, and genetic control. Academic Press, Orlando, FL, p 317

    Google Scholar 

  • Gadbut AP, Toupin DK, Kilbourne EJ, Galper JB (1994) Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscaranic receptor, Gαi2, and the acetylcholine-sensitive K+ channel. J Biol Chem 269:30707–30717

    Google Scholar 

  • Gafvels ME, Paavola LG, Boyd CO, Nolan PM, Wittmaack F, Chawia A, Lazar MZ, Bucan M, Angelin B, Strauss JF (1994) Cloning of a complementary deoxyribonucleic acid encoding the murine homolog of the very low density lipoprotein/apolipoprotein-E receptor: expression pattern and assignment of the gene to mouse chromosome 19 [published erratum appears in Endocrinology 1995 136(2):795]. Endocrinology 135(1):387–394

    Google Scholar 

  • Gilbert W (1978) Why genes in pieces? Nature 271:501

    Google Scholar 

  • Gilbert W (1985) Genes in pieces revisited. Science 228:823–824

    Google Scholar 

  • Goldstein JL, Brown MS, Anderson RGW, Russell DW, Schneider WJ (1985) Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol 1:1–39

    Google Scholar 

  • Gray A, Dull TJ, Ullrich A (1983) Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature 303:722–725

    Google Scholar 

  • Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (1988) 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. EMBO J 7:4119–4127

    Google Scholar 

  • Kallunki P, Tryggvason K (1992) Human basement membrane heparin sulfate proteoglycan core protein: a 467-kd protein containing multiple domains resembling elements of the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. J Cell Biol 116:559–571

    Google Scholar 

  • Kerjaschki D, Farquhar MG (1992) The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA 79:5557–5561

    Google Scholar 

  • Lee LY, Mohler WA, Schafer BL, Freudenberger JS, Byrne-Connolly N, Eager K B, Mosley ST, Leighton JK, Thrift RN, Davis RA, Tanaka RD (1989) Nucleotide sequence of the rat low density lipoprotein receptor cDNA. Nucleic Acids Res 17:1259–1260

    Google Scholar 

  • Mehta KD, Smith M (1989) Identification of an upstream repressor site controlling the expression of an anaerobic gene inS. cerevisiae. J Biol Chem 264:8670–8675

    Google Scholar 

  • Mehta KD, Leung D, Lefebvre L, Smith M (1990) The ANB1 locus ofS. cerevisiae encodes the protein synthesis initiation factor eIF-4D. J Biol Chem 265:8802–8807

    Google Scholar 

  • Mehta KD, Chen WJ, Goldstein JL, Brown M (1991a) The low density lipoprotein receptor inXenopus laevis: five domains that resemble the human receptor. J Biol Chem 266:10406–10414

    Google Scholar 

  • Mehta KD, Brown M, Bilheimer DW, Goldstein JL (1991b) The low density lipoprotein receptor inXenopus laevis: feedback repression mediated by conserved sterol regulatory element. J Biol Chem 266:10415–10419

    Google Scholar 

  • Nagayoshi T, Sanborn D, Hicock NJ, Olsen DR, Fazio MJ, Chu ML, Knowlton R, Mann K, Deutzmann R, Timpl R, Uitto J (1989) Human Nidogen: complete amino acid sequence and structural domains deduced from cDNAs, and evidence for polymorphism of the gene. DNA 8:581–594

    Google Scholar 

  • Nakae H, Sugano M, Ishimori Y, Endo T, Obnita T (1993) Ascidian entactin/nidogen: implication of evolution by shuffling two kinds of cysteine-rich motifs. Eur J Biochem 213:11–19

    Google Scholar 

  • Nimpf J, Stifani S, Bilous PT, Schneider WJ (1994) The somatic cell-specific low density lipoprotein receptor-related protein of the chicken. Close kinship to mammalian low density lipoprotein receptor gene family. J Biol Chem 269:212–219

    Google Scholar 

  • Polvio WJ, Dichek DA, Mason J, Anderson WF (1992) Molecular cloning and nucleotide sequence of cDNA encoding a functional murine low density lipoprotein receptor. Somat Cell Genet 18:443–450

    Google Scholar 

  • Raychowdhury R, Niles JL, McCluskey RT, Smith JA (1989) Autoimmune target in heymann nephritis is a glycoprotein with homology to the LDL receptor. Science 244:1163–1165

    Google Scholar 

  • Russell DW, Brown M, Goldstein JL (1989) Different combinations of cysteine-rich repeats mediate binding of low density lipoprotein receptor to two different proteins. J Biol Chem 264:21682–21688

    Google Scholar 

  • Sakai J, Hoshino A, Sadao T, Miura Y, Ishii H, Suzuki H, Kawarabayasi Y, Yamamoto T (1994) Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene. J Biol Chem 269:2173–2182

    Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    Google Scholar 

  • Schonbaum CP, Lee S, Mahowald AP (1995) The Drosophila yolkless gene encodes a vitellogenin receptor belonging to the low density lipoprotein receptor superfamily. Proc Natl Acad Sci USA 92:1485–1489

    Google Scholar 

  • Stanley KK, Kocher HP, Luzio JP, Jackson P, Tshopp J (1985) The sequence and topology of human complement component C9. EMBO J 4:375–382

    Google Scholar 

  • Stifani S, Nimpf J, Schneider WJ (1990) Vitellogenesis inXenopus laevis and chicken: cognate ligands and oocyte receptors. J Biol Chem 265:882–888

    Google Scholar 

  • Takahashi S, Kawarabayasi Y, Nakai T, Sakai J, Yamamoto T (1992) Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity. Proc Natl Acad Sci USA 89:9252–9256

    Google Scholar 

  • Tensen CP, Kesteren ER, Planta RJ, Cox K, Burke JF, Heerikhuizen H, Vreugdenhil E (1994) A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction. Proc Natl Acad Sci USA 91(11):4816–4820

    Google Scholar 

  • Wessel GM (1995) A protein of the sea urchin cortical granules is targeted to the fertilization envelope and contains an LDL-receptor-like motif. Dev Biol 167:388–397

    Google Scholar 

  • Yamamato T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW (1984) The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell 39:27–38

    Google Scholar 

  • Yochem J, Greenwald I (1993) A gene for a low density lipoprotein receptor-related protein in the nematodeCaenorhabditis elegans. Proc Natl Acad Sci USA 90:4572–4576

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The nucleotide sequence reported will appear in GenBank under accession number L36118

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mehta, K.D., Chang, R. & Norman, J. Chiloscyllium plagiosum low-density lipoprotein receptor: Evolutionary conservation of five different functional domains. J Mol Evol 42, 264–272 (1996). https://doi.org/10.1007/BF02198853

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02198853

Key words

Navigation