PXD035681-2

PXD035681 is an original dataset announced via ProteomeXchange.

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

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.

10.1038/S44320-024-00058-1;

submitter keyword: time-resolved proteomics

protein quality control

mass spectrometry

affinity purification - mass spectrometry

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD035681

PRIDE project URI

• PRIDE
  1. PXD035681
     1. Label: PRIDE project
     2. Name: Time-Resolved Interactome Profiling Deconvolutes Secretory Protein Quality Control Dynamics