PXD058407

PXD058407 is an original dataset announced via ProteomeXchange.

Title	Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism of ubiquitin-independent proteasomal degradation
Description	The 26S proteasome primarily degrades proteins marked by polyubiquitin chains. Although ubiquitin-independent pathways for proteasomal degradation exist, the mechanisms involved remain poorly understood. Bag1 links Hsp70 chaperone to the 26S proteasome, recruiting Hsp70-bound aberrant proteins for degradation. Here, we show that Bag1 interacts with the 26S proteasome through its subunit Rpn1. Using cryo-electron microscopy, we present high-resolution 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 creates a large cavity above the substrate entry gate of the 20S catalytic chamber, enabling the direct entry of Hsp70 clients into the proteolytic chamber. Thus, in this ubiquitin-independent degradation pathway, unfolded proteins skip the need for both client ubiquitination and ATP hydrolysis for degradation.
HostingRepository	PRIDE
AnnounceDate	2025-01-27
AnnouncementXML	Submission_2025-01-27_02:57:04.819.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: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-29 02:03:22	ID requested
⏵ 1	2025-01-27 02:57:05	announced

Dataset with its publication pending

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

Jose Maria Valpuesta
contact affiliation	CNB-CSIC dept. Structure of Macromolecules
contact email	jmv@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/2025/01/PXD058407

PRIDE project URI

• PRIDE
  1. PXD058407
     1. Label: PRIDE project
     2. Name: Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism of ubiquitin-independent proteasomal degradation