Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients.

Abstract

To investigate mechanisms related to functions of the peroxisome targeting signal (PTS) 1 receptor, Pex5p, we analyzed peroxisome matrix protein import in fibroblasts from three patients with peroxisome biogenesis disorders, all with different mutations in the PEX5 gene. The patients 2-01 (Zellweger syndrome) and 2-05 (neonatal adrenoleukodystrophy) have the reported mutations, R390X and N489K, and patient 2-03 (infantile Refsum disease) has a newly identified mutation, S563W. Fibroblasts from 2-03 (S563W) were detected in both PTS1 and PTS2 imports despite the PEX5 defect, findings in contrast with fibroblasts from 2-05 (N489K) severely defective in PTS1 import and those from 2-01 (R390X) severely defective in both PTS1 and PTS2. The PTS1 receptor in 2-03 is functional for only the C-terminal -SKL sequence (acyl-CoA oxidase) and had little or no function for C-terminal -AKL (D-bifunctional protein and sterol carrier protein 2) and -KANL (catalase) sequences, respectively. After transfection of these mutated PEX5 cDNA into the PEX5-defective CHO mutant, transformants of ZP102 revealed that each mutation was responsible for each dysfunction of the PTS1 import. It seems apparent that -AKL and -KANL are poorer variants of PTS1 and are likely to be more susceptible to effects of mutation of its receptor, Pex5p.

• Authors: N Shimozawa, Z Zhang, Y Suzuki, A Imamura, T Tsukamoto, T Osumi, Y Fujiki, T Orii, P G Barth, R J Wanders, N Kondo
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 262 Issue 2 Pg. 504-8 (Aug 27 1999) ISSN: 0006-291X [Print] United States
• PMID: 10462504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 Academic Press.

Chemical References

• Carrier Proteins
• Multienzyme Complexes
• PEX5 protein, human
• Peroxisomal Targeting Signal 2 Receptor
• Peroxisome-Targeting Signal 1 Receptor
• Protein Sorting Signals
• Receptors, Cytoplasmic and Nuclear
• Sterols
• Oxidoreductases
• 17-Hydroxysteroid Dehydrogenases
• 3-Hydroxyacyl CoA Dehydrogenases
• Acyl-CoA Oxidase
• Hydro-Lyases
• Peroxisomal Multifunctional Protein-2
• HSD17B4 protein, human
• Enoyl-CoA Hydratase

Topics

• 17-Hydroxysteroid Dehydrogenases
• 3-Hydroxyacyl CoA Dehydrogenases (metabolism)
• Acyl-CoA Oxidase
• Biological Transport
• Carrier Proteins (metabolism)
• Cell Compartmentation
• Enoyl-CoA Hydratase
• Fibroblasts (cytology)
• Humans
• Hydro-Lyases (metabolism)
• Microbodies (metabolism)
• Multienzyme Complexes (metabolism)
• Mutation
• Oxidoreductases (metabolism)
• Peroxisomal Disorders (genetics)
• Peroxisomal Multifunctional Protein-2
• Peroxisomal Targeting Signal 2 Receptor
• Peroxisome-Targeting Signal 1 Receptor
• Protein Sorting Signals (genetics)
• Receptors, Cytoplasmic and Nuclear (genetics)
• Sterols
• Transformation, Genetic
• Zellweger Syndrome (genetics)