The low density lipoprotein receptor in xenopus laevis I. Five domains that resemble the human receptor

Kamal D. Mehta, Wen Ji Chen, Joseph L. Goldstein, Michael S. Brown

Research output: Contribution to journalArticle

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Abstract

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 ∼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 β-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.

Original languageEnglish (US)
Pages (from-to)10406-10414
Number of pages9
JournalJournal of Biological Chemistry
Volume266
Issue number16
StatePublished - 1991

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LDL Receptors
Xenopus laevis
Xenopus
Genes
Apolipoproteins E
LDL Lipoproteins
Complementary DNA
VLDL Lipoproteins
Amphibians
Sterols
Anura
Cysteine
Animals
Ligands
COS Cells
Haplorhini
Canidae
Tail
Genome
Rabbits

ASJC Scopus subject areas

  • Biochemistry

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The low density lipoprotein receptor in xenopus laevis I. Five domains that resemble the human receptor. / Mehta, Kamal D.; Chen, Wen Ji; Goldstein, Joseph L.; Brown, Michael S.

In: Journal of Biological Chemistry, Vol. 266, No. 16, 1991, p. 10406-10414.

Research output: Contribution to journalArticle

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