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http://purl.uniprot.org/citations/19733220http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19733220http://www.w3.org/2000/01/rdf-schema#comment"

Background

Lens cataract is associated with protein oxidation and aggregation. Two proteins that cause cataract when deleted from the lens are methionine sulfoxide reductase A (MsrA) that repairs protein methionine sulfoxide (PMSO) oxidized proteins and alpha-crystallin which is a two-subunit (alphaA and alphaB) chaperone. Here, we tested whether PMSO formation damages alpha-crystallin chaperone function and whether MsrA could repair PMSO-alpha-crystallin.

Methods

Total alpha-crystallin was oxidized to PMSO and evaluated by CNBr-cleavage and mass spectrometry. Chaperone activity was measured by light scattering using lysozyme as target. PMSO-alpha-crystallin was treated with MsrA, and repair was assessed by CNBr cleavage, mass spectrometry and recovery of chaperone function. The levels of alpha-crystallin-PMSO in the lenses of MsrA-knockout relative to wild-type mice were determined.

Results

PMSO oxidation of total alpha-crystallin (met 138 of alphaA and met 68 of alphaB) resulted in loss of alpha-crystallin chaperone activity. MsrA treatment of PMSO-alpha-crystallin repaired its chaperone activity through reduction of PMSO. Deletion of MsrA in mice resulted in increased levels of PMSO-alpha-crystallin.

Conclusions

Methionine oxidation damages alpha-crystallin chaperone function and MsrA can repair PMSO-alpha-crystallin restoring its chaperone function. MsrA is required for maintaining the reduced state of alpha-crystallin methionines in the lens.

Significance

Methionine oxidation of alpha-crystallin in combination with loss of MsrA repair causes loss of alpha-crystallin chaperone function. Since increased PMSO levels and loss of alpha-crystallin function are hallmarks of cataract, these results provide insight into the mechanisms of cataract development and likely those of other age-related diseases."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.org/dc/terms/identifier"doi:10.1016/j.bbagen.2009.08.011"xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/author"Lee W."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/author"Brennan L.A."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/author"David L.L."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/author"Kantorow M."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/author"Giblin F.J."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/name"Biochim Biophys Acta"xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/pages"1665-1672"xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/title"Methionine sulfoxide reductase A (MsrA) restores alpha-crystallin chaperone activity lost upon methionine oxidation."xsd:string
http://purl.uniprot.org/citations/19733220http://purl.uniprot.org/core/volume"1790"xsd:string
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