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

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.

Adhesion Molecule Expression in Fibroblasts

“…26 We confirmed this phenomenon by showing that only cells overexpressing wt LOX-1 (aa 1 to 273), but not the mutant LOX-1 (aa 1 to 261), could bind DiI-ox-LDL. After ox-LDL treatment, expression of MMP-1, ICAM-1, and VCAM-1 was significantly increased in fibroblasts transfected with CMV-LOX-1 wt but not in those transfected with CMV-LOX-1 .…”

An oxidized low‐density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease

“…9 The lectin-like domain recognizes ligands, and these basic amino-acid residues are important for strengthening ligand binding. 15,16 The Lys-to-Asn change causes reduced binding and internalization of oxidized LDL, suggesting that LOX-1 gene variants may exert a protective effect against atherogenesis. 14,15 As LOX-1 is a receptor for oxidized LDL, this polymorphism may affect the metabolism of oxidized LDL.…”

“…15,16 The Lys-to-Asn change causes reduced binding and internalization of oxidized LDL, suggesting that LOX-1 gene variants may exert a protective effect against atherogenesis. 14,15 As LOX-1 is a receptor for oxidized LDL, this polymorphism may affect the metabolism of oxidized LDL. To examine its effect on oxidized LDL metabolism, we assessed serum MDA-LDL levels.…”

Association of a polymorphism in the 3' untranslated region of the <i>OLR1</i> gene with milk fat and protein in dairy cows

“…Oxidized low density lipoprotein receptor 1 (OLR1) is a type II membrane protein belonging to the C-type lectin family which is encoded by the OLR1 gene (Chen et al 2001). This receptor acts as the major cell surface receptor for oxidized low density lipoprotein (Ox-LDL) (Kataoka et al 2000).…”