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 language | English |
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Pages (from-to) | 269-74 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 383 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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