Our review on recognition and small-molecule mimicry of degrons by E3 ligases is now published in Current Opinion in Structural Biology

  • Graphical Abstract
  • Figure 1.  Structural basis of N-degron recognition.
  • Figure 2.  Structural basis of phosphodegron recognition.
  • Figure 3.  Structural basis of oxygen-dependent degron recognition.
  • Figure 4.  Structural basis of ligand-induced substrate recognition of CRLs.

Well done Xavi!

Read our review here.



  • E3 ligases recruit substrates for proteasomal degradation by recognition of degrons
  • Crystal structures reveal the structural basis and mechanism of degron recognition
  • Small-molecule degron mimetics can prevent or re-direct substrate recognition
  • Small-molecule inducible degrons and PROTACs enable targeted protein degradation



The ubiquitin–proteasome system is a master regulator of protein homeostasis, by which proteins are initially targeted for poly-ubiquitination by E3 ligases and then degraded into short peptides by the proteasome. Nature evolved diverse peptidic motifs, termed degrons, to signal substrates for degradation. We discuss degrons of the N-end rule pathway and also degrons characterized by post-translational modifications, including phosphorylation and hydroxylation. In each case we detail the structural basis of E3 ligase:degron recognition and small-molecule mimicry approaches that disrupt those protein–protein interactions. We present as well genetic and chemical technologies that enable targeted degradation of proteins of interest, namely small-molecule dependent inducible degrons and chemical degraders, for example, proteolysis-targeting chimeras (PROTACs).