Abstract
Mutations in the human DJ-1/PARK7 gene are associated with familial Parkinson’s disease. DJ-1 belongs to a large, functionally diverse family with homologues in all biological kingdoms. Several activities have been demonstrated for DJ-1: an antioxidant protein, a redox-regulated molecular chaperone and a modulator of multiple cellular signalling pathways. The majority of functional studies have focussed on human DJ-1 (hDJ-1), but studies on DJ-1 homologues in Drosophila melanogaster, Caenorhabditis elegans, Dugesia japonica and Escherichia coli also provide evidence of a role for DJ-1 as an antioxidant. Here, we show that dehydration is a potent inducer of a dj-1 gene in the anhydrobiotic nematode Panagrolaimus superbus. Our secondary structure and homology modelling analyses shows that recombinant DJ-1 protein from P. superbus (PsuDJ-1.1) is a well-folded protein, which is similar in structure to the hDJ-1. PsuDJ-1.1 is a heat stable protein; with T1/2 unfolding transition values of 76 and 70 °C obtained from both circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) measurements respectively. We found that PsuDJ-1.1 is an efficient antioxidant that also functions as a ‘holdase’ molecular chaperone that can maintain its chaperone function in a reducing environment. In addition to its chaperone activity, PsuDJ-1.1 may also be an important non-enzymatic antioxidant, capable of providing protection to P. superbus from oxidative damage when the nematodes are in a desiccated, anhydrobiotic state.
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Abbreviations
- BSA:
-
Bovine serum albumin
- CD:
-
Circular dichroism
- CRYAB:
-
αB-crystallin
- CS:
-
Citrate synthase
- DTT:
-
Dithiothreitol
- EST:
-
Expressed sequence tag
- FTIR:
-
Fourier transform infrared spectroscopy
- hDJ-1:
-
Human DJ-1
- HM:
-
Homology model
- MD:
-
Molecular dynamics
- MALDI-ToF MS:
-
Matrix-assisted laser desorption/ionization time of flight mass spectrometry
- MWCO:
-
Molecular weight cut-off
- Ni-NTA:
-
Nickel nitrilotriacetic acid
- PD:
-
Parkinson’s disease
- PsuDJ-1:
-
P. superbus DJ-1
- RMSD:
-
Root mean square deviation
- ROS:
-
Reactive oxygen species.
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Acknowledgments
This project was funded by Science Foundation Ireland (Projects 08/RFP/EOB1660 and 09/RFP/EOB2506). BAC was funded by an Irish Research Council EMBARK post-graduate fellowship. qPCR facilities were funded by Science Foundation Ireland (SFI/07/RFP/GEN/F571/EC07). The AKTA Purifier and MALDI-ToF MS were funded by the Irish Higher Education Authority and the Irish Health Research Board, respectively. The authors wish to acknowledge the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support. The NAMD 2.10 simulation package was developed with NIH support by the Theoretical and Computational Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign.
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Culleton, B.A., Lall, P., Kinsella, G.K. et al. A role for the Parkinson’s disease protein DJ-1 as a chaperone and antioxidant in the anhydrobiotic nematode Panagrolaimus superbus . Cell Stress and Chaperones 20, 121–137 (2015). https://doi.org/10.1007/s12192-014-0531-6
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DOI: https://doi.org/10.1007/s12192-014-0531-6