The LOX-1 scavenger receptor cytoplasmic domain contains a transplantable endocytic motif

Research output: Contribution to journalArticlepeer-review


  • Ravinder Vohra
  • John H Walker
  • Gareth J Howell
  • Shervanthi Homer-Vanniasinkam
  • Sreenivasan Ponnambalam

Colleges, School and Institutes


Oxidized low-density lipoprotein particles is a pro-atherogenic factor implicated in atherosclerotic plaque formation. The LOX-1 scavenger receptor binds OxLDL and is linked to atherosclerotic plaque initiation and progression. We tested the hypothesis that the LOX-1 cytoplasmic domain contains a transplantable signal for membrane protein endocytosis. Structural modeling of the LOX-1 cytoplasmic domain reveals that a tripeptide motif (DDL) implicated in LOX-1 endocytosis is part of a curved beta-pleated sheet structure. The two aspartic acid residues within this structural model are highly solvent-accessible enabling recognition by cytosolic factor(s). A triple alanine substitution of the DDL motif within the LOX-1 scavenger receptor substantially reduced endocytosis of OxLDL. Transplantation of the LOX-1 cytoplasmic domain into a transferrin receptor reporter molecule conferred efficient endocytosis on this hybrid protein. Mutation of the DDL motif within the hybrid LOX-1-TfR protein also substantially reduced receptor-mediated endocytosis. Thus a transplantable endocytic motif within the LOX-1 cytoplasmic domain is needed to ensure efficient internalization of pro-atherogenic OxLDL particles.


Original languageEnglish
Pages (from-to)269-74
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 29 May 2009


  • Endocytosis, Amino Acid Motifs, Humans, Cytoplasm, Scavenger Receptors, Class E, Molecular Sequence Data, Amino Acid Sequence, Protein Structure, Tertiary, Lipoproteins, LDL