title: A role for the Parkinson's disease protein DJ-1 as a chaperone and antioxidant in the anhydrobiotic nematode Panagrolaimus superbus.
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.
authors.affiliation: Department of Biology, National University of Ireland Maynooth, Maynooth, Co Kildare, Ireland.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Culleton
authors.forename: Patrick
authors.initials: P
authors.lastname: Lall
authors.forename: Gemma K
authors.initials: GK
authors.lastname: Kinsella
authors.forename: Sean
authors.initials: S
authors.lastname: Doyle
authors.forename: John
authors.initials: J
authors.lastname: McCaffrey
authors.forename: David A
authors.initials: DA
authors.lastname: Fitzpatrick
authors.forename: Ann M
authors.initials: AM
authors.lastname: Burnell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D015870:Gene Expression; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000502:physiology; D010802:Phylogeny; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D017168:Rhabditida / Q000145:classification / Q000378:metabolism*; D016415:Sequence Alignment; D044366:Transition Temperature
chemical_list: D000975:Antioxidants; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins