4A0A: Structure Of Hsddb1-Drddb2 Bound To A 16 Bp Cpd-Duplex ( Pyrimidine At D-1 Position) At 3.6 A Resolution (Cpd 3)

The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs). The DCAF DDB2 detects UV-induced pyrimidine dimers in the genome and facilitates nucleotide excision repair. We provide the molecular basis for DDB2 receptor-mediated cyclobutane pyrimidine dimer recognition in chromatin. The structures of the fully assembled DDB1-DDB2-CUL4A/B-RBX1 (CRL4(DDB2)) ligases reveal that the mobility of the ligase arm creates a defined ubiquitination zone around the damage, which precludes direct ligase activation by DNA lesions. Instead, the COP9 signalosome (CSN) mediates the CRL4(DDB2) inhibition in a CSN5 independent, nonenzymatic, fashion. In turn, CSN inhibition is relieved upon DNA damage binding to the DDB2 module within CSN-CRL4(DDB2). The Cockayne syndrome A DCAF complex crystal structure shows that CRL4(DCAF(WD40)) ligases share common architectural features. Our data support a general mechanism of ligase activation, which is induced by CSN displacement from CRL4(DCAF) on substrate binding to the DCAF.
PDB ID: 4A0ADownload
MMDB ID: 95450
PDB Deposition Date: 2011/9/8
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4A0A: tetrameric; determined by software (PISA)
Molecular Components in 4A0A
Label Count Molecule
Proteins (2 molecules)
DNA Damage-binding Protein 1(Gene symbol: DDB1)
Molecule annotation
DNA Damage-binding Protein 2(Gene symbol: ddb2)
Molecule annotation
Nucleotides(2 molecules)
Molecule annotation
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB