1SOA

Human DJ-1 with sulfinic acid

Summary for 1SOA

• Entry DOI: 10.2210/pdb1soa/pdb
• Related: 1p5f
• Descriptor: RNA-binding protein regulatory subunit; oncogene DJ1 (2 entities in total)
• Functional Keywords: parkinson's disease, dj-1/thij/pfpi familiy, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Lipid-anchor : Q99497
• Total number of polymer chains: 1
• Total formula weight: 19949.05

Authors

Canet-Aviles, R.,Wilson, M.A.,Miller, D.W.,Ahmad, R.,McLendon, C.,Bandyopadhyay, S.,Baptista, M.J.,Ringe, D.,Petsko, G.A.,Cookson, M.R. (deposition date: 2004-03-13, release date: 2004-06-22, Last modification date: 2024-10-30)

Primary citation

Wilson, M.A.,Miller, D.W.,Ahmad, R.,McLendon, C.,Bandyopadhyay, S.,Baptista, M.J.,Ringe, D.,Petsko, G.A.,Cookson, M.R.
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.
Proc.Natl.Acad.Sci.USA, 101:9103-9108, 2004

PubMed Abstract: 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.

PubMed: 15181200
DOI: 10.1073/pnas.0308089100

Experimental method

X-RAY DIFFRACTION (1.2 Å)