{"title":"DEGRONOPEDIA: A practical guide to identifying and targeting protein degrons.","authors":"Natalia A Szulc, Wojciech Pokrzywa","doi":"10.1016/bs.mie.2025.06.014","DOIUrl":null,"url":null,"abstract":"<p><p>Degrons are recognition motifs mediating substrate binding to E3 ubiquitin ligases within the ubiquitin-proteasome system, driving protein ubiquitination and degradation. These motifs, located at protein N- and C-termini or within internal regions, are essential for maintaining proteostasis. Effective degradation relies on a tripartite architecture: a degron motif, a ubiquitination site, and a proteasomal unwinding seed. This chapter introduces DEGRONOPEDIA, a web server for identifying and predicting degrons across eukaryotic proteomes. It integrates machine learning, solvent accessibility modeling, and proteolysis simulations to analyze degrons in sequential and structural contexts. We provide detailed guidance on its workflow and applications, highlighting its role in studying terminal and internal degrons.</p>","PeriodicalId":18662,"journal":{"name":"Methods in enzymology","volume":"719 ","pages":"67-94"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Methods in enzymology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.mie.2025.06.014","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/5 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Degrons are recognition motifs mediating substrate binding to E3 ubiquitin ligases within the ubiquitin-proteasome system, driving protein ubiquitination and degradation. These motifs, located at protein N- and C-termini or within internal regions, are essential for maintaining proteostasis. Effective degradation relies on a tripartite architecture: a degron motif, a ubiquitination site, and a proteasomal unwinding seed. This chapter introduces DEGRONOPEDIA, a web server for identifying and predicting degrons across eukaryotic proteomes. It integrates machine learning, solvent accessibility modeling, and proteolysis simulations to analyze degrons in sequential and structural contexts. We provide detailed guidance on its workflow and applications, highlighting its role in studying terminal and internal degrons.
期刊介绍：
The critically acclaimed laboratory standard for almost 50 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Each volume is eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with over 500 volumes the series contains much material still relevant today and is truly an essential publication for researchers in all fields of life sciences, including microbiology, biochemistry, cancer research and genetics-just to name a few. Five of the 2013 Nobel Laureates have edited or contributed to volumes of MIE.
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