RT Journal Article
SR Electronic
T1 DEGRONOPEDIA - a web server for proteome-wide inspection of degrons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.19.492622
DO 10.1101/2022.05.19.492622
A1 Natalia A. Szulc
A1 Filip Stefaniak
A1 Małgorzata Piechota
A1 Andrea Cappannini
A1 Janusz M. Bujnicki
A1 Wojciech Pokrzywa
YR 2022
UL http://biorxiv.org/content/early/2022/05/22/2022.05.19.492622.abstract
AB The ubiquitin-proteasome system is a proteolytic pathway that removes damaged and unwanted proteins. Their selective turnover is initiated by ubiquitin (Ub) attachment, mainly by Ub ligases that recognize substrates through their short linear motifs termed degrons. A degradation-targeting degron comprises a nearby Ub-modified residue and an intrinsically disordered region (IDR) involved in interaction with the proteasome. Degron-signaling has been studied over the last decades, yet there are no resources for systematic screening of degron sites to facilitate studies on their biological significance, such as targeted protein degradation approaches. To bridge this gap, we developed DEGRONOPEDIA, a web server that allows exploration of degron motifs in the proteomes of seven model organisms and maps these data to Lys, Cys, Thr, and Ser residues that can undergo ubiquitination and to IDRs proximal to them, both in sequence and structure. The server also reports the post-translational modifications and pathogenic mutations within the degron and its flanking regions, as these can modulate the degron’s accessibility. Degrons often occur at the amino or carboxyl end of a protein substrate, acting as initiators of the N-/C-degron pathway, respectively. Therefore, since they may appear following the protease cleavage, DEGRONOPEDIA simulate sequence nicking based on experimental data and theoretical predictions and screen for emerging degron motifs. Moreover, we implemented machine learning to predict the stability of the N-/C-termini, facilitating the identification of substrates of the N-/C-degron pathways. We are confident that our tool will stimulate research on degron-signaling providing output information in a ready-to-validate context. DEGRONOPEDIA can be freely accessed at degronopedia.com.Competing Interest StatementThe authors have declared no competing interest.