1soa
From Proteopedia
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Human DJ-1 with sulfinic acid
Contents |
Overview
Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease., The function of DJ-1 is unknown, but an acidic isoform accumulates after, oxidative stress, leading to the suggestion that DJ-1 is protective under, these conditions. We addressed whether this represents a posttranslational, modification at cysteine residues by systematically mutating cysteine, residues in human DJ-1. WT or C53A DJ-1 was readily oxidized in cultured, cells, generating a pI 5.8 isoform, but an artificial C106A mutant was, not. We observed a cysteine-sulfinic acid at C106 in crystalline DJ-1 but, no modification of C53 or C46. Oxidation of DJ-1 was promoted by the, crystallization procedure. In addition, oxidation-induced mitochondrial, relocalization of DJ-1 and protection against cell death were abrogated in, C106A but not C53A or C46A. We suggest that DJ-1 protects against neuronal, death, and that this is signaled by acidification of the key cysteine, residue, C106.
Disease
Known diseases associated with this structure: Amyotrophic lateral sclerosis-Parkinsonism/dementia complex 2 OMIM:[602533], Parkinson disease 7, autosomal recessive early-onset OMIM:[602533]
About this Structure
1SOA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization., Canet-Aviles RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR, Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8. Epub 2004 Jun 4. PMID:15181200
Page seeded by OCA on Mon Nov 12 19:16:12 2007
