Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding

M. Chen, S. Narumiya, T. Masaki, T. Sawamura

Research output: Contribution to journalArticle

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Abstract

Lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) is a cell-surface endocytosis receptor for atherogenic oxLDL, which is highly expressed in endothelial cells. Recent studies suggest that it may play significant roles in atherogenesis. LOX-1 is a type-II membrane protein that structurally belongs to the C-type lectin family molecules. This study was designed to characterize the specific domain on LOX-1 that recognizes oxLDL. Truncation of the lectin domain of LOX-1 abrogated oxLDL-binding activity. Deletion of the utmost C-terminal ten amino acid residues (261-270) was enough to disrupt the oxLDL-binding activity. Substitutions of Lys-262 and/or Lys-263 with Ala additively attenuated the activity. Serial-deletion analysis showed that residues up to 265 are required for the expression of minimal binding activity, although deletion of the C-terminal three residues (268-270) still retained full binding activity. Consistently, these alterations in LOX-1 impaired the recognition by a functionally blocking monoclonal antibody for LOX-1. These data demonstrated the distinct role of the lectin domain as the functional domain recognizing LOX-1 ligand. The conserved C-terminal residues of lectin-like domain are essential for binding oxLDL. Particularly, the basic amino acid pair is important for the binding.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalBiochemical Journal
Volume355
Issue number2
DOIs
StatePublished - Apr 15 2001
Externally publishedYes

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Keywords

  • Epitope mapping
  • Lectin-like oxidized LDL receptor-1
  • Monoclonal antibody

ASJC Scopus subject areas

  • Biochemistry

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