Dimerization of Parkinson's disease - causing DJ-1 and formation of high molecular weight complexes in human brain

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-1(WT), DJ-1(L166P), and a newly identified disease-causing mutant DJ-1(M26I) 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-1(WT) and mutant DJ-1(M26I) were present as stable homodimers; DJ-1(L166P) in particular tended to form high-order complexes as well. In contrast to DJ-1(L166P) that is quickly degraded by the proteasome, DJ-1(M26B) 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. (C) 2004 Elsevier Inc. All rights reserved.