Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase

Cell. 2006 Jan 13;124(1):105-17. doi: 10.1016/j.cell.2005.10.033.


The DDB1-Cul4A ubiquitin ligase complex promotes protein ubiquitination in diverse cellular functions and is reprogrammed by the V proteins of paramyxoviruses to degrade STATs and block interferon signaling. Here we report the crystal structures of DDB1 alone and in complex with the simian virus 5 V protein. The DDB1 structure reveals an intertwined three-propeller cluster, which contains two tightly coupled beta propellers with a large pocket in between and a third beta propeller flexibly attached on the side. The rigid double-propeller fold of DDB1 is targeted by the viral V protein, which inserts an entire helix into the double-propeller pocket, whereas the third propeller domain docks DDB1 to the N terminus of the Cul4A scaffold. Together, these results not only provide structural insights into how the virus hijacks the DDB1-Cul4A ubiquitin ligase but also establish a structural framework for understanding the multiple functions of DDB1 in the uniquely assembled cullin-RING E3 machinery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Crystallization
  • Crystallography, X-Ray
  • Cullin Proteins / chemistry*
  • Cullin Proteins / genetics
  • Cullin Proteins / physiology
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / physiology
  • Genes, Viral*
  • Humans
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Protein Structure, Tertiary*
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology
  • Viral Structural Proteins / chemistry*
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / physiology


  • CUL4A protein, human
  • Cullin Proteins
  • DDB1 protein, human
  • DNA-Binding Proteins
  • V protein, Simian parainfluenza virus 5
  • Viral Structural Proteins
  • Ubiquitin-Protein Ligases

Associated data

  • PDB/2B5L
  • PDB/2B5M
  • PDB/2B5N