title: Dimerization of Parkinson's disease-causing DJ-1 and formation of high molecular weight complexes in human brain.
abstract: Mutations in the DJ-1 gene have been implicated in the PARK7-linked autosomal recessive form of Parkinson's disease (PD). The molecular properties of DJ-1WT, DJ-1L166P, and a newly identified disease-causing mutant DJ-1M26I were explored after they were transiently expressed in mammalian cells. Treatment of intact, living cells with the chemical crosslinker disuccinimidyl suberate (DSS) revealed that DJ-1WT and mutant DJ-1M26I were present as stable homodimers; DJ-1L166P in particular tended to form high-order complexes as well. In contrast to DJ-1L166P that is quickly degraded by the proteasome, DJ-1M26I was found to be an efficiently expressed and stable variant of DJ-1, suggesting that these mutations have distinct biochemical effects on DJ-1. We further provide evidence that in human brain, under nondenaturing conditions, DJ-1 is present in high molecular weight (HMW) complexes of approximately 250-700 kDa containing parkin, another PD-associated protein.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baulac
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: LaVoie
authors.forename: Jennifer
authors.initials: J
authors.lastname: Strahle
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schlossmacher
authors.forename: Weiming
authors.initials: W
authors.lastname: Xia
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D019281:Dimerization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008970:Molecular Weight; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1