Structure of the TXNL1-bound proteasome

Proteasomes degrade diverse proteins in different cellular contexts through incompletely defined regulatory mechanisms. Here, we report the cryo-EM structure of thioredoxin-like protein 1 (TXNL1) bound to the 19S regulatory particle of proteasomes via interactions with PSMD1/Rpn2, PSMD4/Rpn10, and PSMD14/Rpn11. These interactions are necessary for the ubiquitin-independent degradation of TXNL1 upon cellular exposure to metal- or metalloid-containing oxidative agents, thereby establishing a structural basis for the stress-induced degradation of TXNL1.