Expanding the E3 Ligase Toolbox: Structural Validation of DCAF2 as a Novel Adaptor for Targeted Protein Degradation

  • Reveal high-resolution cryo-EM structures of the DCAF2:DDB1:DDA1 complex to elucidate ligand binding and substrate recruitment mechanisms
  • Demonstrate covalent fragment engagement of C141 and degrader-mediated ternary complex formation driving BRD4 ubiquitination and degradation
  • Discuss how structural and functional validation of DCAF2 expands the usable E3 ligase repertoire for next-generation molecular glue and degrader design