PXD019427

PXD019427 is an original dataset announced via ProteomeXchange.

Title	Comparative Thyroglobulin Interactome Profiling
Description	Thyroglobulin (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.
HostingRepository	PRIDE
AnnounceDate	2020-11-20
AnnouncementXML	Submission_2020-11-20_06:36:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Madison Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-27 17:15:48	ID requested
⏵ 1	2020-11-20 06:36:17	announced

Wright MT, Kouba L, Plate L, Thyroglobulin interactome profiling defines altered proteostasis topology associated with thyroid dyshormonogenesis. Mol Cell Proteomics, ():(2020) [pubmed]

submitter keyword: AP-MS, interactomics, protein quality control, thyroglobulin, congenital hypothyroidism, proteostasis, quantitative proteomics, protein folding

Lars Plate
contact affiliation	Assistant Professor Departments of Chemistry and Biological Sciences Vanderbilt Unversity
contact email	lars.plate@vanderbilt.edu
lab head
Madison Wright
contact affiliation	Vanderbilt University Department of Chemistry
contact email	madison.t.wright@vanderbilt.edu
dataset submitter

Dataset FTP location

PRIDE project URI

• PRIDE
  1. PXD019427
     1. Label: PRIDE project
     2. Name: Comparative Thyroglobulin Interactome Profiling