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

Vohra, RS; Walker, JH; Howell, GJ; Homer-Vanniasinkam, S; Ponnambalam, S; (2009) The LOX-1 scavenger receptor cytoplasmic domain contains a transplantable endocytic motif. BIOCHEM BIOPH RES CO , 383 (2) 269 - 274. 10.1016/j.bbrc.2009.04.012.

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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. (C) 2009 Elsevier Inc. All rights reserved.

Type:Article
Title:The LOX-1 scavenger receptor cytoplasmic domain contains a transplantable endocytic motif
DOI:10.1016/j.bbrc.2009.04.012
Keywords:LOX-1, Endocytosis, Oxidized LDL particle, Acidic motif, LOW-DENSITY-LIPOPROTEIN, LECTIN-LIKE DOMAIN, LDL RECEPTOR-1, BINDING, ATHEROSCLEROSIS, RESIDUES, CELLS, LOCALIZATION, RECOGNITION, SEQUENCES
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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