4A08

Structure of hsDDB1-drDDB2 bound to a 13 bp CPD-duplex (purine at D-1 position) at 3.0 A resolution (CPD 1)

Summary for 4A08

• Entry DOI: 10.2210/pdb4a08/pdb
• Related: 2B5L 2B5M 2B5N 2HYE 3EI1 3EI2 3EI3 3EI4 4A09 4A0A 4A0B 4A0K 4A0L 4A11
• Descriptor: DNA DAMAGE-BINDING PROTEIN 1, DNA DAMAGE-BINDING PROTEIN 2, 5'-D(*AP*CP*GP*CP*GP*AP*(TTD)P*GP*CP*GP*CP*CP*C)-3', ... (7 entities in total)
• Functional Keywords: dna-binding protein-dna complex, dna damage repair, dna-binding protein/dna
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 181741.11

Authors

Scrima, A.,Fischer, E.S.,Iwai, S.,Gut, H.,Thoma, N.H. (deposition date: 2011-09-08, release date: 2011-11-30, Last modification date: 2023-12-20)

Primary citation

Scrima, A.,Fischer, E.S.,Iwai, S.,Gut, H.,Thoma, N.H.
The Molecular Basis of Crl4(Ddb2/Csa) Ubiquitin Ligase Architecture, Targeting, and Activation
Cell(Cambridge,Mass.), 147:1024-, 2011

PubMed Abstract: 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.

PubMed: 22118460
DOI: 10.1016/J.CELL.2011.10.035

Experimental method

X-RAY DIFFRACTION (3 Å)