4A0L

Structure of DDB1-DDB2-CUL4B-RBX1 bound to a 12 bp abasic site containing DNA-duplex

Summary for 4A0L

• Entry DOI: 10.2210/pdb4a0l/pdb
• Related: 2B5L 2B5M 2B5N 2HYE 3EI1 3EI2 3EI3 3EI4 4A08 4A09 4A0A 4A0B 4A0C 4A0K
• Descriptor: DNA DAMAGE-BINDING PROTEIN 1, DNA DAMAGE-BINDING PROTEIN 2, CULLIN-4B, ... (6 entities in total)
• Functional Keywords: ligase-dna-binding protein-dna complex, ligase/dna-binding protein/dna
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 12
• Total formula weight: 548735.52

Authors

Fischer, E.S.,Scrima, A.,Gut, H.,Thoma, N.H. (deposition date: 2011-09-09, release date: 2011-12-14, Last modification date: 2023-12-20)

Primary citation

Fischer, E.S.,Scrima, A.,Bohm, K.,Matsumoto, S.,Lingaraju, G.M.,Faty, M.,Yasuda, T.,Cavadini, S.,Wakasugi, M.,Hanaoka, F.,Iwai, S.,Gut, H.,Sugasawa, K.,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 (7.4 Å)