PXD002658

PXD002658 is an original dataset announced via ProteomeXchange.

Title	Lens Disulfide crosslink
Description	Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract (ARNC). To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathione-depleted LEGSKO mouse lenses for intra- vs. intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was ~4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H2O2, while γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33 and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130 and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose C42, C79/80, C154 in γC; C42, C33 in γD, and C83, C115 and C130 in γS. In conclusion, while the β-crystallin disulfidome is highly conserved in ARNC and LEGSKO mouse, and reproducible by in vitro oxidation, some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of ARNC.
HostingRepository	PRIDE
AnnounceDate	2015-10-16
AnnouncementXML	Submission_2015-10-16_02:03:35.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD002658
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xingjun Fan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Dimethyl; ICAT-C:13C(9); ICAT-C; Oxidation; Acetyl; Carbamidomethyl
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-04 02:11:36	ID requested
⏵ 1	2015-10-16 02:03:36	announced

Fan X, Zhou S, Wang B, Hom G, Guo M, Li B, Yang J, Vaysburg D, Monnier VM, -Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens. Mol Cell Proteomics, 14(12):3211-23(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: lens, cataract, disulfide bond

Xingjun Fan
contact affiliation	Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
contact email	xxf3@case.edu
lab head
Xingjun Fan
contact affiliation	Case Western Reserve University
contact email	xxf3@case.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002658
     1. Label: PRIDE project
     2. Name: Lens Disulfide crosslink