Systematic prediction of degrons and E3 ubiquitin ligase binding via deep learning.

Journal: BMC biology
PMID:

Abstract

BACKGROUND: Degrons are short linear motifs, bound by E3 ubiquitin ligase to target protein substrates to be degraded by the ubiquitin-proteasome system. Mutations leading to deregulation of degron functionality disrupt control of protein abundance due to mistargeting of proteins destined for degradation and often result in pathologies. Targeting degrons by small molecules also emerges as an exciting drug design strategy to upregulate the expression of specific proteins. Despite their essential function and disease targetability, reliable identification of degrons remains a conundrum. Here, we developed a deep learning-based model named Degpred that predicts general degrons directly from protein sequences.

Authors

  • Chao Hou
    Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Yuxuan Li
    Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • Mengyao Wang
    Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
  • Hong Wu
    Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Tingting Li
    Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, Dalian, China.