The atomic resolution crystal structure of the YajL (ThiJ) protein from Escherichia coli: A close prokaryotic homologue of the Parkinsonism-associated protein DJ-1

Mark A. Wilson, Dagmar Ringe, Gregory A. Petsko

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The Escherichia coli protein YajL (ThiJ) is a member of the DJ-1 superfamily with close homologues in many prokaryotes. YajL also shares 40% sequence identity with human DJ-1, an oncogene and neuroprotective protein whose loss-of-function mutants are associated with certain types of familial, autosomal recessive Parkinsonism. We report the 1.1 Å resolution crystal structure of YajL in a crystal form with two molecules in the asymmetric unit. The structure of YajL is remarkably similar to that of human DJ-1 (0.9 Å Cα RMSD) and both proteins adopt the same dimeric structure. The conserved cysteine residue located in the "nucleophile elbow" is oxidized to either cysteine sulfenic or sulfinic acid in the two molecules in the asymmetric unit, and a mechanism for this oxidation is proposed that may be valid for other proteins in the DJ-1 superfamily as well. Rosenfield difference matrix analysis of the refined anisotropic displacement parameters in the YajL structure reveals significant differences in the intramolecular flexibility of the two non-crystallographic symmetry-related molecules in the asymmetric unit. Lastly, a comparison of the crystal structures of the four different E. coli members of the DJ-1 superfamily indicates that the variable oligomerization in this superfamily is due to a combination of protein-specific insertions into the core fold that form specific interfaces while occluding others plus optimization of residues in the structurally invariant regions of the core fold that facilitate protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)678-691
Number of pages14
JournalJournal of Molecular Biology
Volume353
Issue number3
DOIs
StatePublished - Oct 28 2005

Keywords

  • Cysteine oxidation
  • DJ-1 superfamily
  • Parkinson's disease
  • Protein-protein interaction

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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