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PXD009199

PXD009199 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMapping Ubiquitination Sites in Alzheimer's Disease
DescriptionAlzheimer’s Disease (AD) is characterized by the deposition of protein aggregates such as neurofibrillary tangles (NFTs) and amyloid (Aβ) plaques in the brain. Post-translational modification through ubiquitylationplays critical roles in clearing misfolded protein aggregates. Investigating global ubiquitylation changes inAD brain may provide insights regarding the underlying mechanisms of proteostasis and disease pathogenesis.Here, we utilizedan immunoaffinity approach to specifically enrichubiquitinated(di-glycine) peptides frompostmortemhuman control and AD braintissues.Mass spectrometry(MS)based proteomicanalysis identified global ubiquitylation changes associated with ADand hierarchical clustering of the human brain ubiquitylome clearly classified AD cases from healthy controls based on ubiquitylation patterns. Polyubiquitin linkage analysis identified increased levels of all seven polyubiquitin linkage typesas well as total ubiquitin in the AD brain tissues.We also report novel ubiquitylation sites in the microtubulebinding repeatof Tauwith potential implicationsfor Tauaggregation. Dually modified peptides with both phosphorylation and ubiquitylationsites, many of which originated from Tauprotein are also differentially enriched in AD.Furthermore, all the KXGS motifswithin themicrotubule binding region (MTBR)of Tauprotein,which represents the core ofNFTs,are enriched among dually modified peptides. Collectively, these studieshighlight the utility of an immunoaffinity enrichment approach coupled with MSanalysis for mapping AD associated global ubiquitylome changesas well as to gain insights intounderlying proteostasis pathwaysaltered in AD brain.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:43:43.676.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Dammer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine; phosphorylated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-03-13 08:18:12ID requested
12019-06-25 03:18:22announced
22024-10-22 04:43:51announced2024-10-22: Updated project metadata.
Publication List
10.1002/pmic.201800108;
Abreha MH, Dammer EB, Ping L, Zhang T, Duong DM, Gearing M, Lah JJ, Levey AI, Seyfried NT, Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease. Proteomics, 18(20):e1800108(2018) [pubmed]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: ubiquitylome,AD, GG remnant peptides
Contact List
Nicholas T. Seyfried
contact affiliationEmory University School of Medicine Department of Biochemistry
contact emailnseyfri@emory.edu
lab head
Eric Dammer
contact affiliationEmory University
contact emailedammer@emory.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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