The low density lipoprotein receptor. Identification of amino acids in cytoplasmic domain required for rapid endocytosis.

C. G. Davis, I. R. van Driel, D. W. Russell, M. S. Brown, J. L. Goldstein

Research output: Contribution to journalArticlepeer-review

206 Scopus citations

Abstract

The 50-residue cytoplasmic domain of the low density lipoprotein receptor (amino acids 790-839) directs the receptor to coated pits, thereby facilitating rapid endocytosis of bound low density lipoprotein. To determine the structural features required for this targeting, we produced 24 mutations in the cytoplasmic domain through use of oligonucleotide-directed mutagenesis. The first 22 amino acids of the cytoplasmic domain (residues 790-811) are sufficient for rapid internalization. The amino acid at position 807 is especially critical. Aromatic residues (tyrosine, phenylalanine, or tryptophan) at this position allow rapid internalization. Charged or uncharged aliphatic residues do not substitute. Although the requirements at the neighboring positions (806 and 808) are less stringent, the insertion of proline at position 806 is detrimental. These specificities suggest that the juxtamembranous region of the cytoplasmic domain participates in protein:protein interactions that allow the low density lipoprotein receptor to cluster in coated pits.

Original languageEnglish (US)
Pages (from-to)4075-4082
Number of pages8
JournalJournal of Biological Chemistry
Volume262
Issue number9
StatePublished - Mar 25 1987

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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