9PMJ

Human 19S proteasome bound to TXNL1 PITH domain without C-terminus

This is a non-PDB format compatible entry.

Summary for 9PMJ

• Entry DOI: 10.2210/pdb9pmj/pdb
• EMDB information: 71737
• Descriptor: 26S proteasome regulatory subunit 7, 26S proteasome non-ATPase regulatory subunit 11, 26S proteasome non-ATPase regulatory subunit 6, ... (23 entities in total)
• Functional Keywords: proteasome, 19s, rp, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 19
• Total formula weight: 936711.14

Authors

Chen, X.,Negi, H.,Walters, K.J. (deposition date: 2025-07-17, release date: 2026-07-01, Last modification date: 2026-07-29)

Primary citation

Lee, K.,Negi, H.,Chen, X.,Atallah-Yunes, K.,Truslow, S.,Castelino, R.E.,Guest, M.R.,Ciancone, A.M.,Lu, X.,Tarasov, S.G.,Chari, R.,Walters, K.J.,O'Reilly, F.J.
Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy.
Mol.Cell, 2026

PubMed Abstract: Molecular machines rely on dynamic, low-affinity interactions to perform their functional roles. We developed PhIX-MS (photo-induced in situ crosslinking-mass spectrometry), a structural proteomics workflow to capture topological information for such transient interactions in cells by UV-activated crosslinking. Applying PhIX-MS with cryo-electron microscopy (cryo-EM) to proteasomes, we mapped the redox sensor TXNL1 at the proteasome regulatory particle (RP), including its dynamic thioredoxin-like domain near RPN2/PSMD1 and RPN13/ADRM1, where it is ideal for reducing substrates prior to proteolysis. RPs without the proteolytic core particle (CP) were structurally resolved while bound to TXNL1 and/or the chaperone PSMD5/S5b, which inserts its C terminus into the ATPase pore, causing extensive structural rearrangements. Additionally, PhIX-MS and AlphaFold identified the ubiquitin ligase UBE3C/Hul5 at RPN2, RPN3, and a dynamic RPN10 region, tethering UBE3C above the substrate entry channel. Our integrative approach enables the localization of native, low-affinity protein interactions and is broadly applicable to dynamic macromolecular assemblies.

PubMed: 42476128
DOI: 10.1016/j.molcel.2026.06.032

Experimental method

ELECTRON MICROSCOPY (4.22 Å)