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Targeting of the human adrenoleukodystrophy protein to the peroxisomal membrane by an internal region containing a highly conserved motif

Landgraf, P, Mayerhofer, PU, Polanetz, R, Roscher, AA and Holzinger, A (2003) Targeting of the human adrenoleukodystrophy protein to the peroxisomal membrane by an internal region containing a highly conserved motif Eur J Cell Biol, 82. pp. 401-410.

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Abstract

In this study we addressed the targeting requirements of peroxisomal ABC transporters, in particular the human adrenoleukodystrophy protein. This membrane protein is defective or missing in X-linked adrenoleukodystrophy, a neurodegenerative disorder predominantly presenting in childhood. Using adrenoleukodystrophy protein deletion constructs and green fluorescent protein fusion constructs we identified the amino acid regions 1-110 and 67-164 to be sufficient for peroxisomal targeting. However, the minimal region shared by these constructs (amino acids 67-110) is not sufficient for peroxisomal targeting by itself. Additionally, the NH2-terminal 66 amino acids enhance targeting efficiency. Green fluorescent protein-labeled fragments of human peroxisomal membrane protein 69 and Saccharomyces cerevisiae Pxa1 corresponding to the amino acid 67-164 adrenoleukodystrophy protein region were also directed to the mammalian peroxisome. The required region contains a 14-amino-acid motif (71-84) conserved between the adrenoleukodystrophy protein and human peroxisomal membrane protein 69 and yeast Pxa1. Omission or truncation of this motif in the adrenoleukodystrophy protein abolished peroxisomal targeting. The single amino acid substitution L78F resulted in a significant reduction of targeting efficiency. The in-frame deletion of three amino acids (del78-80LLR) within the proposed targeting motif in two patients suffering from X-linked adrenoleukodystrophy resulted in the mislocalization of a green fluorescent protein fusion protein to nucleus, cytosol and mitochondria. Our data define the targeting region of human adrenoleukodystrophy protein containing a highly conserved 14-amino-acid motif.

Item Type: Article
Authors :
NameEmailORCID
Landgraf, PUNSPECIFIEDUNSPECIFIED
Mayerhofer, PUp.mayerhofer@surrey.ac.ukUNSPECIFIED
Polanetz, RUNSPECIFIEDUNSPECIFIED
Roscher, AAUNSPECIFIEDUNSPECIFIED
Holzinger, AUNSPECIFIEDUNSPECIFIED
Date : 2003
Identification Number : 10.1078/0171-9335-00331
Uncontrolled Keywords : ATP-Binding Cassette Transporters/biosynthesis/*genetics/metabolism Adrenoleukodystrophy/*genetics/metabolism Amino Acid Sequence Animals Green Fluorescent Proteins Humans Luminescent Proteins Molecular Sequence Data Peroxisomes/*metabolism Recombinant Fusion Proteins/genetics/metabolism Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics/metabolism Sequence Homology, Amino Acid
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:42
Last Modified : 17 May 2017 14:51
URI: http://epubs.surrey.ac.uk/id/eprint/828854

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