DEGRONOPEDIA: a web server for proteome-wide inspection of degrons

Abstract

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.

Cellular N-myristoyl transferases Are Required for Mammarenavirus Multiplication

“…However, it is highly unlikely that the HA tag influenced the outcome of the experiment, since growth kinetics and peak titers of the rLCMV-Z-HA were not significantly affected. Bioinformatic analysis revealed that HA-tagged both Z-WT and Z-G2A mutant proteins have five putative degrons [63].The functional degron region, which includes parts of the tripartite model and the tertiary structure necessary for E3 ligase engagement, is predicted to be located within 40 amino acids of the degron motif, whereas the HA tag was positioned more than 50 amino acids away from lysine 38 (K38) of the degron motif, supporting the exclusion of HA as an interfering factor. Moreover, experimental evidence supports that the HA tag does not interfere with C-terminal degrons in other proteins across different systems of eukaryotes [64][65][66][67], and we have shown that LCMV Z protein with a Cterminal HA tag is fully functional in cell-based assays virus [68].…”