Summary information and primary citation

PDB-id
4a0l; SNAP-derived features in text and JSON formats; DNAproDB
Class
ligase-DNA-binding protein-DNA
Method
X-ray (7.4 Å)
Summary
Structure of ddb1-ddb2-cul4b-rbx1 bound to a 12 bp abasic site containing DNA-duplex
Reference
Fischer ES, Scrima A, Bohm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thoma NH (2011): "The Molecular Basis of Crl4(Ddb2/Csa) Ubiquitin Ligase Architecture, Targeting, and Activation." Cell(Cambridge,Mass.), 147, 1024. doi: 10.1016/J.CELL.2011.10.035.
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.

Cartoon-block schematics in six views (download the tarball)

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