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
{"title":"Structure of the TXNL1-bound proteasome","authors":"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","doi":"10.1038/s41594-025-01639-w","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"65 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature structural & molecular biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41594-025-01639-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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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