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DEGRONOPEDIA: a web server for proteome-wide inspection of degrons
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2024-04-03 , DOI: 10.1093/nar/gkae238
Natalia A Szulc 1 , Filip Stefaniak 2 , Małgorzata Piechota 1 , Anna Soszyńska 1 , Gabriela Piórkowska 1 , Andrea Cappannini 2 , Janusz M Bujnicki 2 , Chiara Maniaci 3 , Wojciech Pokrzywa 1
Affiliation  

E3 ubiquitin ligases recognize substrates through their short linear motifs termed degrons. While degron-signaling has been a subject of extensive study, resources for its systematic screening are limited. To bridge this gap, we developed DEGRONOPEDIA, a web server that searches for degrons and maps them to nearby residues that can undergo ubiquitination and disordered regions, which may act as protein unfolding seeds. Along with an evolutionary assessment of degron conservation, the server also reports on post-translational modifications and mutations that may modulate degron availability. Acknowledging the prevalence of degrons at protein termini, DEGRONOPEDIA incorporates machine learning to assess N-/C-terminal stability, supplemented by simulations of proteolysis to identify degrons in newly formed termini. An experimental validation of a predicted C-terminal destabilizing motif, coupled with the confirmation of a post-proteolytic degron in another case, exemplifies its practical application. DEGRONOPEDIA can be freely accessed at degronopedia.com.

中文翻译:

DEGRONOPEDIA:用于蛋白质组范围内降解决定子检查的网络服务器

E3 泛素连接酶通过称为降解决定子的短线性基序识别底物。虽然降解决定子信号传导已成为广泛研究的主题,但用于系统筛选的资源却有限。为了弥补这一差距,我们开发了 DEGRONOPEDIA,这是一种网络服务器,可以搜索降解决定子并将其映射到附近可以进行泛素化的残基和无序区域,这些残基可以充当蛋白质展开种子。除了对降解决定子保守性进行进化评估外,服务器还报告可能调节降解决定子可用性的翻译后修饰和突变。 DEGRONOPEDIA 认识到蛋白质末端降解决定子的普遍存在,因此采用机器学习来评估 N-/C-末端稳定性,并辅以模拟蛋白水解来识别新形成的末端中的降解决定子。对预测的 C 端不稳定基序的实验验证,加上在另一个案例中对蛋白水解后降解决定子的确认,例证了其实际应用。 DEGRONOPEDIA 可以在 degronopedia.com 上免费访问。
更新日期:2024-04-03
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