PXD075459-1

PXD075459 is an original dataset announced via ProteomeXchange.

Title	Uncovering the Unexpected Role of Proteasome Activator PA200 in Regulating Immunoproteasome Expression and Activity
Description	The proteasome activator PA200 binds to the catalytic core of both standard proteasome (s20S) and the immunoproteasome (i20S); however, whether PA200 uses the same mechanisms to activate i20S remains unknown. Our cryo-EM structures of the singly- and doubly-capped i20S-PA200 complexes and in vitro assays here reveals that binding of the first PA200 induces an allosteric bending of the i20S and widening of the opposite unbound α-ring. This results in a higher binding occupancy of the i20S and stronger activation compared to the s20S. In addition, PA200 preferentially alters i20S proteolytic output by increasing peptide generation and shifting cleavage specificity toward caspase-like activity. We also show that in cells and tissues that express PA200, s20S and i20S, PA200 binds more efficiently to the i20S than to the s20S. Intriguingly, the expression of PA200 and the catalytic subunits of the i20S are differentially regulated, with PA200 playing a potential role in controlling the i20S subunits’ expression. This suggests that i20S function is fine-tuned by differential expression of PA200, and reveals an additional layer of i20S regulation.
HostingRepository	PRIDE
AnnounceDate	2026-05-28
AnnouncementXML	Submission_2026-05-28_08:13:14.638.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amélie Bosc-Rosati
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-10 12:59:55	ID requested
⏵ 1	2026-05-28 08:13:15	announced
2	2026-06-04 00:48:45	announced	2026-06-04: Updated project metadata.
3	2026-06-04 01:40:04	announced	2026-06-04: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, TimsTOF, DIA, LC-MS

Dr Odile Schiltz
contact affiliation	Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Toulouse, 31077, France
contact email	Odile.Schiltz@ipbs.fr
lab head
Amélie Bosc-Rosati
contact affiliation	IPBS
contact email	amelie.bosc-rosati@ipbs.fr
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/2026/05/PXD075459

PRIDE project URI

• PRIDE
  1. PXD075459
     1. Label: PRIDE project
     2. Name: Uncovering the Unexpected Role of Proteasome Activator PA200 in Regulating Immunoproteasome Expression and Activity