Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

PeerJ

article

Wouter Boomsma¹  Sofie V. Nielsen¹  Kresten Lindorff-Larsen¹  Rasmus Hartmann-Petersen¹  Lars Ellgaard¹ 

[1] Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen

关键词: E3 ligase;    Hrd1;    San1;    Intrinsic disorder;    STUbL;    Ubiquitin;    Protein folding;    Protein degradation;    Quality control;   

DOI  :  10.7717/peerj.1725

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work indicates that San1 is not a unique case, and that several other yeast and human E3 ligases have sequence properties that may allow them to recognize substrates by a similar mechanism as San1.

【 授权许可】

CC BY