scholarly journals Predicting the Function and Subcellular Location ofCaenorhabditis elegansProteins Similar toSaccharomyces cerevisiaeβ-Oxidation Enzymes

Yeast ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 188-200 ◽  
Author(s):  
Aner Gurvitz ◽  
Sigrid Langer ◽  
Martin Piskacek ◽  
Barbara Hamilton ◽  
Helmut Ruis ◽  
...  
Keyword(s):  
Zellweger Syndrome ◽  
Model Organism ◽  
Subcellular Location ◽  
Peroxisomal Disorders ◽  
C Elegans ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal

The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose usingCaenorhabditis elegansas a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identifiedC. elegansPEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p–SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list ofC. elegansproteins with similarities to well-characterized yeast β-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes.C. elegansmight emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a β-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

scholarly journals Predicting the Function and Subcellular Location of Caenorhabditis elegans Proteins Similar to Saccharomyces cerevisiae β-Oxidation Enzymes

Yeast ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 188-200
Author(s):  
Aner Gurvitz ◽  
Sigrid Langer ◽  
Martin Piskacek ◽  
Barbara Hamilton ◽  
Helmut Ruis ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Zellweger Syndrome ◽  
Model Organism ◽  
Subcellular Location ◽  
Peroxisomal Disorders ◽  
C Elegans ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal

The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose using Caenorhabditis elegans as a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identified C. elegans PEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p–SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list of C. elegans proteins with similarities to well-characterized yeast β-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes. C. elegans might emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a β-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

scholarly journals Recognition of Peroxisomal Targeting Signal Type 1 by the Import Receptor Pex5p

2001 ◽  
Vol 276 (18) ◽  
pp. 15034-15041 ◽  
Author(s):  
André T. J. Klein ◽  
Phil Barnett ◽  
Gina Bottger ◽  
Daphne Konings ◽  
Henk F. Tabak ◽  
...  
Keyword(s):  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal ◽  
Peroxisomal Targeting Signal ◽  
Import Receptor

scholarly journals Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Fabian Schueren ◽  
Thomas Lingner ◽  
Rosemol George ◽  
Julia Hofhuis ◽  
Corinna Dickel ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
In Silico ◽  
Stop Codon ◽  
The Other ◽  
Translational Readthrough ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal ◽  
Peroxisomal Targeting Signal

Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB is targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit, into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes.

scholarly journals Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders.

1995 ◽  
Vol 130 (1) ◽  
pp. 51-65 ◽  
Author(s):  
E A Wiemer ◽  
W M Nuttley ◽  
B L Bertolaet ◽  
X Li ◽  
U Francke ◽  
...  
Keyword(s):  
Protein Import ◽  
Zellweger Syndrome ◽  
Complementation Group ◽  
Cell System ◽  
Peroxisomal Disorders ◽  
Peroxisomal Membrane ◽  
Peroxisomal Protein ◽  
Peroxisomal Targeting ◽  
Targeting Signal

Two peroxisomal targeting signals, PTS1 and PTS2, are involved in the import of proteins into the peroxisome matrix. Human patients with fatal generalized peroxisomal deficiency disorders fall into at least nine genetic complementation groups. Cells from many of these patients are deficient in the import of PTS1-containing proteins, but the causes of the protein-import defect in these patients are unknown. We have cloned and sequenced the human cDNA homologue (PTS1R) of the Pichia pastoris PAS8 gene, the PTS1 receptor (McCollum, D., E. Monosov, and S. Subramani. 1993. J. Cell Biol. 121:761-774). The PTS1R mRNA is expressed in all human tissues examined. Antibodies to the human PTS1R recognize this protein in human, monkey, rat, and hamster cells. The protein is localized mainly in the cytosol but is also found to be associated with peroxisomes. Part of the peroxisomal PTS1R protein is tightly bound to the peroxisomal membrane. Antibodies to PTS1R inhibit peroxisomal protein-import of PTS1-containing proteins in a permeabilized CHO cell system. In vitro-translated PTS1R protein specifically binds a serine-lysine-leucine-peptide. A PAS8-PTS1R fusion protein complements the P. pastoris pas8 mutant. The PTS1R cDNA also complements the PTS1 protein-import defect in skin fibroblasts from patients--belonging to complementation group two--diagnosed as having neonatal adrenoleukodystrophy or Zellweger syndrome. The PTS1R gene has been localized to a chromosomal location where no other peroxisomal disorder genes are known to map. Our findings represent the only case in which the molecular basis of the protein-import deficiency in human peroxisomal disorders is understood.

Components Involved in Peroxisome Import, Biogenesis, Proliferation, Turnover, and Movement

1998 ◽  
Vol 78 (1) ◽  
pp. 171-188 ◽  
Author(s):  
SURESH SUBRAMANI
Keyword(s):  
Protein Import ◽  
Protein Translocation ◽  
Peroxisomal Disorders ◽  
Peroxisomal Membrane ◽  
Peroxisomal Protein ◽  
Peroxisomal Targeting ◽  
Docking Proteins ◽  
Targeting Signal ◽  
Peroxisomal Targeting Signal

Subramani, Suresh. Components Involved in Peroxisome Import, Biogenesis, Proliferation, Turnover, and Movement. Physiol. Rev. 78: 171–188, 1998. — In the decade that has elapsed since the discovery of the first peroxisomal targeting signal (PTS), considerable information has been obtained regarding the mechanism of protein import into peroxisomes. The PTSs responsible for the import of matrix and membrane proteins to peroxisomes, the receptors for several of these PTSs, and docking proteins for the PTS1 and PTS2 receptors are known. Many peroxins involved in peroxisomal protein import and biogenesis have been characterized genetically and biochemically. These studies have revealed important new insights regarding the mechanism of protein translocation across the peroxisomal membrane, the conservation of PEX genes through evolution, the role of peroxins in fatal human peroxisomal disorders, and the biogenesis of the organelle. It is clear that peroxisomal protein import and biogenesis have many features unique to this organelle alone. More recent studies on peroxisome degradation, division, and movement highlight newer aspects of the biology of this organelle that promise to be just as exciting and interesting as import and biogenesis.

scholarly journals A novel dynein-type AAA+ protein with peroxisomal targeting signal type 2

2020 ◽  
Vol 167 (5) ◽  
pp. 429-432
Author(s):  
Tsuneo Imanaka ◽  
Kosuke Kawaguchi
Keyword(s):  
Mammalian Cells ◽  
Ring Structure ◽  
Family Protein ◽  
Peroxisomal Targeting ◽  
Signal Type ◽  
Targeting Signal ◽  
Aaa Protein ◽  
Peroxisomal Targeting Signal

Abstract Peroxisomal matrix proteins are imported into peroxisomes in a process mediated by peroxisomal targeting signal (PTS) type 1 and 2. The PTS2 proteins are imported into peroxisomes after binding with Pex7p. Niwa et al. (A newly isolated Pex7-binding, atypical PTS2 protein P7BP2 is a novel dynein-type AAA+ protein. J Biochem 2018;164:437–447) identified a novel Pex7p-binding protein in CHO cells and characterized the subcellular distribution and molecular properties of the human homologue, ‘P7BP2’. Interestingly, P7BP2 possesses PTS2 at the NH2 terminal and six putative AAA+ domains. Another group has suggested that the protein also possesses mitochondrial targeting signal at the NH2 terminal. In fact, the P7BP2 expressed in mammalian cells is targeted to both peroxisomes and mitochondria. The purified protein from Sf9 cells is a monomer and has a disc-like ring structure, suggesting that P7BP2 is a novel dynein-type AAA+ family protein. The protein expressed in insect cells exhibits ATPase activity. P7BP2 localizes to peroxisomes and mitochondria, and has a common function related to dynein-type ATPases in both organelles.

Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p involved in shuttling of the PTS1 receptor Pex5p in peroxisome biogenesis

2008 ◽  
Vol 36 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Yukio Fujiki ◽  
Non Miyata ◽  
Naomi Matsumoto ◽  
Shigehiko Tamura
Keyword(s):  
Atp Hydrolysis ◽  
Zellweger Syndrome ◽  
Complementation Group ◽  
Peroxisome Biogenesis ◽  
Aaa Atpase ◽  
Causal Genes ◽  
Signal Type ◽  
Targeting Signal ◽  
Membrane Bound

The peroxisome is a single-membrane-bound organelle found in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient PBDs (peroxisome biogenesis disorders), such as Zellweger syndrome. Two AAA (ATPase associated with various cellular activities) peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for CG (complementation group) 1 and CG4 PBDs respectively. PEX26, which is responsible for CG8 PBDs, codes for Pex26p, the recruiter of Pex1p–Pex6p complexes to peroxisomes. We recently assigned the binding regions between human Pex1p and Pex6p and elucidated the pivotal roles that the AAA cassettes, D1 and D2 domains, play in Pex1p–Pex6p interaction and in peroxisome biogenesis. ATP binding to both AAA cassettes of Pex1p and Pex6p was a prerequisite for the Pex1p–Pex6p interaction and peroxisomal localization, but ATP hydrolysis by the D2 domains was not required. Pex1p exists in two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, with these possibly having distinct functions in peroxisome biogenesis. AAA peroxins are involved in the export from peroxisomes of Pex5p, the PTS1 (peroxisome-targeting signal type 1) receptor.

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