Crystal Structure of Filamentous Aggregates of Human DJ-1 Formed in an Inorganic Phosphate-dependent Manner
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- Crystal Structure of Filamentous Aggregates of Human DJ-1 Formed in an Inorganic Phosphate-dependent Manner
- Cha, Sun-Shin; Il Jung, Ha; Jeon, Hyesung; An, Young Jun; Kim, In-Kwon; Yun, Sanguk; Ahn, Hyun Jin; Chung, Kwang Chul; Lee, Sang Hee; Suh, Pann-Ghill; Kang, Sa-Ouk
- Issue Date
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.49, pp.34069 - 34075
- Mutations in the DJ-1 gene have been implicated in the autosomal recessive early onset parkinsonism. DJ-1 is a soluble dimeric protein with critical roles in response to oxidative stress and in neuronal maintenance. However, several lines of evidence suggest the existence of a nonfunctional aggregated form of DJ-1 in the brain of patients with some neurodegenerative diseases. Here, we show that inorganic phosphate, an important anion that exhibits elevated levels in patients with Parkinson disease, transforms DJ-1 into filamentous aggregates. According to the 2.4-A crystal structure, DJ-1 dimers are linearly stacked through Pi-mediated interactions to form protofilaments, which are then bundled into a filamentous assembly.
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