Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner

Sun Shin Cha, Il Jung Ha, Hyesung Jeon, Jun An Young, In Kwon Kim, Sanguk Yun, Jin Ahn Hyun, Chul Chung Kwang, Hee Lee Sang, Pann Ghill Suh, Sa Ouk Kang

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14 Citations (Scopus)

Abstract

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-Å crystal structure, DJ-1 dimers are linearly stacked through Pi-mediated interactions to form protofilaments, which are then bundled into a filamentous assembly.

Original languageEnglish
Pages (from-to)34069-34075
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number49
DOIs
Publication statusPublished - 2008 Dec 5

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Cha, S. S., Ha, I. J., Jeon, H., Young, J. A., Kim, I. K., Yun, S., Hyun, J. A., Kwang, C. C., Sang, H. L., Suh, P. G., & Kang, S. O. (2008). Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner. Journal of Biological Chemistry, 283(49), 34069-34075. https://doi.org/10.1074/jbc.M804243200