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

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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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
Volume383
Issue number2
DOIs
Publication statusPublished - 29 May 2009

Keywords

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

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