PXD035681 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Time-Resolved Interactome Profiling Deconvolutes Secretory Protein Quality Control Dynamics |
Description | Protein-protein interactions play host to several cellular processes that depend heavily on both spatial and temporal regulation of these interactions. As such, understanding these parameters is necessary to fully comprehend and elucidate cellular processes and pathological disease states associated with them. Many advancements have allowed for more detailed characterization of these parameters, yet none are available to identify and quantify de novo protein-protein interactions with time-resolution at an organelle-wide scale. To address this, we have developed a quantitative mass-spectrometry method, time-resolved interactome profiling (TRIP). As a proof of concept, we utilize this methodology to elucidate alterations in interactions for the protein folding disease congenital hypothyroidism. We identify and deconvolute altered temporal engagement with pathways such as Hsp70/90 assisted folding, disulfide/redox processing, and N-glcosylation associated with hypothyroidism pathophysiology. We have coupled this methodology with functional siRNA screening and identified Vcp and Tex264 as key protein degradation components whose inhibition rescues mutant prohormone secretion. Ultimately, our results provide insight into the temporal coordination of protein homeostasis, and our TRIP method should find broad application in investigating other protein folding diseases and cellular processes. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:52:54.926.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Madison Wright |
SpeciesList | scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMTpro; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-01 09:16:36 | ID requested | |
1 | 2024-08-08 02:56:22 | announced | |
⏵ 2 | 2024-10-22 06:52:55 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: time-resolved proteomics |
protein quality control |
mass spectrometry |
affinity purification - mass spectrometry |
Contact List
Lars Plate |
contact affiliation | Vanderbilt University Department of Chemistry Department of Biological Sciences |
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035681
- Label: PRIDE project
- Name: Time-Resolved Interactome Profiling Deconvolutes Secretory Protein Quality Control Dynamics