The low density lipoprotein receptor in Xenopus laevis. I. Five domains that resemble the human receptor.
All five functional domains of the low density lipoprotein (LDL) receptor were assembled in their modern form more than 350 million years ago, as revealed from the sequence of two cloned cDNAs from the frog Xenopus laevis. The two cDNAs appear to represent duplicated copies of the LDL receptor gene that arose when the entire genome of Xenopus duplicated approximately 30 million years ago. Both frog LDL receptors bound Xenopus LDL with high affinity and human LDL with lower affinity when expressed in monkey COS cells. The receptors also showed high affinity for rabbit beta-migrating very low density lipoprotein and canine apoE-HDLc, both of which contain apolipoprotein E. Each of the seven cysteine-rich repeats in the ligand binding domain of the Xenopus receptors resembles its counterpart in the human, indicating that these repeats had already acquired their independent structures by the time of amphibian development. The cytoplasmic tail of both Xenopus receptors is 86% identical to the human, including the FDNPVY sequence necessary for internalization in coated pits. The attainment of a fully developed receptor structure in Xenopus suggests that earlier forms of the receptor may exist in animals that are older than amphibians. An accompanying paper demonstrates that expression of both Xenopus receptor genes is controlled by a sterol regulatory element that closely resembles the human sequence (Mehta, K.D., Brown, M.S., Bilheimer, D.W., and Goldstein, J.L. (1991) J. Biol. Chem. 266, 10415-10419).
Mehta
K D
KD
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Chen
W J
WJ
Goldstein
J L
JL
Brown
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015152:Blotting, Northern; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008322:Mammals; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012313:RNA / Q000032:analysis; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014982:Xenopus laevis
D008077:Lipoproteins, LDL; D015345:Oligonucleotide Probes; D011973:Receptors, LDL; D012313:RNA; D004247:DNA