PXD069071

PXD069071 is an original dataset announced via ProteomeXchange.

Title	Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism for direct transfer of substrates to the catalytic chamber
Description	Coupling of the degradation and chaperone systems, particularly under cellular stress, is essential for eliminating unfolded proteins. The co-chaperone Bag1 links the Hsp70 chaperone to the 26S proteasome, recruiting Hsp70-bound unfolded proteins for proteasomal degradation. Here, we present cryo-EM structures of the Bag1-bound 26S proteasome, which reveal unprecedented conformational changes within the 19S regulatory particle. Bag1 binding to the Rpn1 subunit induces a dramatic reconfiguration of AAA+ ATPase subunits, disrupting the canonical spiral staircase conformation and remodeling the central channel architecture. This reconfiguration generates a large cavity above the substrate entry gate of the 20S core particle (CP). Additionally, our structures highlight key roles for the conserved pore-2 loops of ATPases Rpt2 and Rpt5 in opening the gate of the 20S CP, enabling direct translocation of Hsp70 clients into the proteolytic chamber independently of ubiquitination. Thus, these findings suggest a new mechanism of the proteasomal degradation, by which remodeling the central cavity and 20S gate in the presence of Bag1, possibly bypassing the need for ubiquitination and ATPase motor function.
HostingRepository	PRIDE
AnnounceDate	2025-12-23
AnnouncementXML	Submission_2025-12-23_01:54:02.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jimena Muntaner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-02 02:45:24	ID requested
⏵ 1	2025-12-23 01:54:03	announced

Dataset with its publication pending

submitter keyword: chaperones, degradation, Hsp70, Bag1,Proteasome

Jorge Cuellar
contact affiliation	Centro Nacional de Biotecnología (CNB-CSIC), Madrid, España.
contact email	jcuellar@cnb.csic.es
lab head
Jimena Muntaner
contact affiliation	Centro Nacional de Biotecnología (CNB-CSIC)
contact email	jimena.muntaner@cnb.csic.es
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/2025/12/PXD069071

PRIDE project URI

• PRIDE
  1. PXD069071
     1. Label: PRIDE project
     2. Name: Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism for direct transfer of substrates to the catalytic chamber