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PXD019427

PXD019427 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleComparative Thyroglobulin Interactome Profiling
DescriptionThyroglobulin (Tg) is a secreted iodoglycoprotein serving as the precursor for T3 and T4 hormones. Many characterized Tg gene mutations produce secretion-defective variants resulting in congenital hypothyroidism (CH). Tg processing and secretion is controlled by extensive interactions with chaperones, trafficking, and degradation proteins comprising the secretory proteostasis network. While dependencies on individual pro-teostasis network components are known, the integration of proteostasis pathways mediating Tg protein quality control and the molecular basis of mutant Tg misprocessing remain poorly understood. We employ a multiplexed quantitative affinity purification–mass spectrometry approach to define the Tg proteostasis interactome and changes between WT and several CH-variants. Mutant Tg processing is associated with common imbalances in proteostasis engagement including increased chaperoning, oxidative folding, and routing towards ER-associated degradation components, yet variants are inefficiently degraded. Furthermore, we reveal mutation-specific changes in engagement with N-glycosylation components, suggesting distinct requirements of one Tg variant on dual engagement of both oligosaccharyltransferase complex isoforms for degradation. Modulating dysregulated proteostasis components and pathways may serve as a therapeutic strategy to restore Tg secretion and thyroid hormone biosynthesis.
HostingRepositoryPRIDE
AnnounceDate2020-11-20
AnnouncementXMLSubmission_2020-11-20_06:36:15.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMadison Wright
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF; Orbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-27 17:15:48ID requested
12020-11-20 06:36:17announced
Publication List
Wright MT, Kouba L, Plate L, Thyroglobulin interactome profiling defines altered proteostasis topology associated with thyroid dyshormonogenesis. Mol Cell Proteomics, ():(2020) [pubmed]
Keyword List
submitter keyword: AP-MS, interactomics, protein quality control, thyroglobulin, congenital hypothyroidism, proteostasis, quantitative proteomics, protein folding
Contact List
Lars Plate
contact affiliationAssistant Professor Departments of Chemistry and Biological Sciences Vanderbilt Unversity
contact emaillars.plate@vanderbilt.edu
lab head
Madison Wright
contact affiliationVanderbilt University Department of Chemistry
contact emailmadison.t.wright@vanderbilt.edu
dataset submitter
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