Structural effects of Parkinson's disease linked DJ-1 mutations. Academic Article uri icon

Overview

abstract

  • Mutations in the protein DJ-1 are associated with familial forms of Parkinson's disease, indicating that DJ-1 may be involved in pathways related to the etiology of this disorder. Here we have used solution state NMR and circular dichroism spectroscopies to evaluate the extent of structural perturbations associated with five different Parkinson's disease linked DJ-1mutations: L166P, E64D, M26I, A104T, and D149A. Comparison of the data with those obtained for the wild-type protein shows that the L166P mutation leads to severe and global destabilization and unfolding of the protein structure, while the structure of the E64D mutation, as expected, is nearly unperturbed. Interestingly, the remaining three mutants all show different degrees of structural perturbation, which are accompanied by a reduction in the thermodynamic stability of the protein. The observed structural and thermodynamic differences are likely to underlie any functional variations between these mutants and the wild type, which in turn are likely responsible for the pathogenicity of these mutations.

publication date

  • May 1, 2008

Research

keywords

  • Intracellular Signaling Peptides and Proteins
  • Mutation
  • Oncogene Proteins
  • Parkinson Disease

Identity

PubMed Central ID

  • PMC2327288

Scopus Document Identifier

  • 43049119301

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.0020362

PubMed ID

  • 18436956

Additional Document Info

volume

  • 17

issue

  • 5