Culleton Bridget A, Lall Patrick, Kinsella Gemma K, Doyle Sean, McCaffrey John, Fitzpatrick David A, Burnell Ann M
Department of Biology, National University of Ireland Maynooth, Maynooth, Co Kildare, Ireland.
Cell Stress Chaperones. 2015 Jan;20(1):121-37. doi: 10.1007/s12192-014-0531-6. Epub 2014 Oct 16.
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.
人类DJ-1/PARK7基因的突变与家族性帕金森病相关。DJ-1属于一个庞大的、功能多样的家族,在所有生物界中都有同源物。DJ-1已被证明具有多种活性:一种抗氧化蛋白、一种氧化还原调节分子伴侣以及多种细胞信号通路的调节剂。大多数功能研究都集中在人类DJ-1(hDJ-1)上,但对黑腹果蝇、秀丽隐杆线虫、日本三角涡虫和大肠杆菌中DJ-1同源物的研究也提供了DJ-1作为抗氧化剂发挥作用的证据。在这里,我们表明脱水是兼性厌氧线虫秀丽隐杆线虫中dj-1基因的有效诱导剂。我们的二级结构和同源性建模分析表明,来自秀丽隐杆线虫的重组DJ-1蛋白(PsuDJ-1.1)是一种折叠良好的蛋白,其结构与hDJ-1相似。PsuDJ-1.1是一种热稳定蛋白;通过圆二色性(CD)和傅里叶变换红外光谱(FTIR)测量分别获得的T1/2解折叠转变值为76和70°C。我们发现PsuDJ-1.1是一种有效的抗氧化剂,还可作为“保持酶”分子伴侣,在还原环境中维持其伴侣功能。除了其伴侣活性外,PsuDJ-1.1还可能是一种重要的非酶抗氧化剂,当线虫处于干燥的兼性厌氧状态时,能够保护秀丽隐杆线虫免受氧化损伤。