Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이공주 | - |
dc.contributor.author | 신동해 | - |
dc.date.accessioned | 2021-11-09T16:31:00Z | - |
dc.date.available | 2021-11-09T16:31:00Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.issn | 1470-8728 | - |
dc.identifier.other | OAK-30281 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/259201 | - |
dc.description.abstract | DJ-1 is known to play neuroprotective roles by eliminating reactive oxygen species (ROS) as an antioxidant protein. However, the molecular mechanism of DJ-1 function has not been well elucidated. This study explored the structural and functional changes of DJ-1 in response to oxidative stress. Human DJ-1 has three cysteine residues (Cys46, Cys53 and Cys106). We found that, in addition to Cys106, Cys46 is the most reactive cysteine residue in DJ-1, which was identified employing an NPSB-B chemical probe (Ctag) that selectively reacts with redox-sensitive cysteine sulfhydryl. Peroxidatic Cys46 readily formed an intra-disulfide bond with adjacent resolving Cys53, which was identified with nanoUPLC-ESI-q-TOF tandem mass spectrometry (MS/MS) employing DBond algorithm under the non-reducing condition. Mutants (C46A and C53A), not forming Cys46-Cys53 disulfide cross-linking, increased oxidation of Cys106 to sulfinic and sulfonic acids. Furthermore, we found that DJ-1 C46A mutant has distorted unstable structure identified by biochemical assay and employing hydrogen/deuterium exchange-mass spectrometry (HDX-MS) analysis. All three Cys mutants lost antioxidant activities in SN4741 cell, a dopaminergic neuronal cell, unlike WT DJ-1. These findings suggest that all three Cys residues including Cys46-Cys53 disulfide cross-linking are required for maintaining the structural integrity, the regulation process and cellular function as an antioxidant protein. These studies broaden the understanding of regulatory mechanisms of DJ-1 that operate under oxidative conditions. | - |
dc.language | English | - |
dc.publisher | PORTLAND PRESS LTD | - |
dc.title | Stepwise oxidations play key roles in the structural and functional regulations of DJ-1 | - |
dc.type | Article | - |
dc.relation.issue | 19 | - |
dc.relation.volume | 478 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 3505 | - |
dc.relation.lastpage | 3525 | - |
dc.relation.journaltitle | BIOCHEMICAL JOURNAL | - |
dc.identifier.doi | 10.1042/BCJ20210245 | - |
dc.identifier.wosid | WOS:000705677900002 | - |
dc.identifier.scopusid | 2-s2.0-85118097411 | - |
dc.author.google | Song, In-Kang | - |
dc.author.google | Kim, Mi-Sun | - |
dc.author.google | Ferrell, James E., Jr. | - |
dc.author.google | Shin, Dong-Hae | - |
dc.author.google | Lee, Kong-Joo | - |
dc.contributor.scopusid | 이공주(7501497635;57191532162) | - |
dc.contributor.scopusid | 신동해(57217374185) | - |
dc.date.modifydate | 20230208115507 | - |