Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner.
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 P(i)-mediated interactions to form protofilaments, which are then bundled into a filamentous assembly.
Mesh Terms:
Brain, Crystallization, Crystallography, X-Ray, Dimerization, Humans, Intracellular Signaling Peptides and Proteins, Light, Microscopy, Electron, Molecular Conformation, Oncogene Proteins, Parkinson Disease, Phosphates, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Scattering, Radiation
Brain, Crystallization, Crystallography, X-Ray, Dimerization, Humans, Intracellular Signaling Peptides and Proteins, Light, Microscopy, Electron, Molecular Conformation, Oncogene Proteins, Parkinson Disease, Phosphates, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Scattering, Radiation
J. Biol. Chem.
Date: Dec. 05, 2008
PubMed ID: 18922803
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