3I8E: Crystal Structure Of Ddb1 In Complex With The H-Box Motif Of Wdr42a

The cullin 4-DNA-damage-binding protein 1 (CUL4-DDB1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. Here we report the crystal structure of DDB1 in complex with a central fragment of hepatitis B virus X protein (HBx), whose DDB1-binding activity is important for viral infection. The structure reveals that HBx binds DDB1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus SV5-V protein despite their sequence divergence. Our structure-based functional analysis suggests that, like SV5-V, HBx captures DDB1 to redirect the ubiquitin ligase activity of the CUL4-DDB1 E3 ligase. We also identify the alpha-helical motif shared by these viral proteins in the cellular substrate-recruiting subunits of the E3 complex, the DDB1-CUL4-associated factors (DCAFs) that are functionally mimicked by the viral hijackers. Together, our studies reveal a common yet promiscuous structural element that is important for the assembly of cellular and virally hijacked CUL4-DDB1 E3 complexes.
PDB ID: 3I8EDownload
MMDB ID: 78594
PDB Deposition Date: 2009/7/9
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 3I8E: dimeric; determined by author and by software (PISA)
Molecular Components in 3I8E
Label Count Molecule
Proteins (2 molecules)
DNA Damage-binding Protein 1(Gene symbol: DDB1)
Molecule annotation
WD Repeat-containing Protein 42A(Gene symbol: DCAF8)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB