DCAF8 binds DDB1 via an N-terminal helix-loop-helix motif to assemble CRL4 and promote cell cycle progression - PubMed
4 hours ago
- #CRL4 ubiquitin ligase
- #cryo-EM structure
- #cell cycle regulation
- The cryo-EM structure of DCAF8 bound to DDB1 reveals an N-terminal helix-loop-helix (HLH) motif driving their interaction.
- This HLH motif fits into a conserved pocket formed by DDB1's BPA and BPC domains, and disrupting this interface impairs complex assembly and cell cycle progression.
- Disruption of the DCAF8-DDB1 interface reduces CDC25A ubiquitination and leads to cell cycle defects, while the double DxR box in DCAF8 is not critical for DDB1 binding.
- The findings establish a distinct recruitment mechanism for DCAF8 within CRL4 ubiquitin ligase complexes, enhancing substrate specificity through DCAFs.