Jingjing Gao, Christopher Nardone, Matthew C. J. Yip, Haruka Chino, Xin Gu, Zachary Mirman, Michael J. Rale, Joao A. Paulo, Stephen J. Elledge, Sichen Shao
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Proteasomes degrade diverse proteins in different cellular contexts through incompletely defined regulatory mechanisms. Here we report the cryo-EM structure of human thioredoxin-like protein 1 (TXNL1) bound to the 19S regulatory particle of proteasomes via interactions with PSMD1 (Rpn2), PSMD4 (Rpn10) and PSMD14 (Rpn11). Proteasome binding is necessary for the ubiquitin-independent degradation of TXNL1 upon cellular exposure to metal- or metalloid-containing oxidative agents, thereby establishing a structural requirement for the stress-induced degradation of TXNL1.
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