1soa
From Proteopedia
(New page: 200px<br /> <applet load="1soa" size="450" color="white" frame="true" align="right" spinBox="true" caption="1soa, resolution 1.20Å" /> '''Human DJ-1 with sul...) |
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| - | [[Image:1soa.gif|left|200px]]<br /> | + | [[Image:1soa.gif|left|200px]]<br /><applet load="1soa" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1soa" size=" | + | |
caption="1soa, resolution 1.20Å" /> | caption="1soa, resolution 1.20Å" /> | ||
'''Human DJ-1 with sulfinic acid'''<br /> | '''Human DJ-1 with sulfinic acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SOA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1SOA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SOA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ahmad, R.]] | [[Category: Ahmad, R.]] | ||
[[Category: Bandyopadhyay, S.]] | [[Category: Bandyopadhyay, S.]] | ||
| - | [[Category: Baptista, M | + | [[Category: Baptista, M J.]] |
[[Category: Canet-Aviles, R.]] | [[Category: Canet-Aviles, R.]] | ||
| - | [[Category: Cookson, M | + | [[Category: Cookson, M R.]] |
[[Category: McLendon, C.]] | [[Category: McLendon, C.]] | ||
| - | [[Category: Miller, D | + | [[Category: Miller, D W.]] |
| - | [[Category: Petsko, G | + | [[Category: Petsko, G A.]] |
[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
| - | [[Category: Wilson, M | + | [[Category: Wilson, M A.]] |
[[Category: dj-1/thij/pfpi familiy]] | [[Category: dj-1/thij/pfpi familiy]] | ||
[[Category: parkinson's disease]] | [[Category: parkinson's disease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:33 2008'' |
Revision as of 13:03, 21 February 2008
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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
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