Gao Jingjing, Nardone Christopher, Yip Matthew C J, Chino Haruka, Gu Xin, Mirman Zachary, Rale Michael J, Paulo Joao A, Elledge Stephen J, Shao Sichen
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nat Struct Mol Biol. 2025 Aug 6. doi: 10.1038/s41594-025-01639-w.
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.
蛋白酶体通过尚未完全明确的调控机制在不同细胞环境中降解多种蛋白质。在此，我们报告了人硫氧还蛋白样蛋白1（TXNL1）与蛋白酶体19S调节颗粒结合的冷冻电镜结构，该结合通过与PSMD1（Rpn2）、PSMD4（Rpn10）和PSMD14（Rpn11）的相互作用实现。当细胞暴露于含金属或类金属的氧化试剂时，蛋白酶体结合对于TXNL1不依赖泛素的降解是必需的，从而确立了TXNL1应激诱导降解的结构要求。
