2HYE

Crystal Structure of the DDB1-Cul4A-Rbx1-SV5V Complex

Summary for 2HYE

• Entry DOI: 10.2210/pdb2hye/pdb
• Descriptor: DNA damage-binding protein 1, Nonstructural protein V, Cullin-4A, ... (5 entities in total)
• Functional Keywords: beta propeller, ring finger, zinc finger, propeller cluster, helical repeats, cullin repeats, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q16531 P62877; Host cytoplasm : P11207
• Total number of polymer chains: 4
• Total formula weight: 251513.86

Authors

Angers, S.,Li, T.,Yi, X.,MacCoss, M.J.,Moon, R.T.,Zheng, N. (deposition date: 2006-08-05, release date: 2006-10-03, Last modification date: 2024-10-30)

Primary citation

Angers, S.,Li, T.,Yi, X.,MacCoss, M.J.,Moon, R.T.,Zheng, N.
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.
Nature, 443:590-593, 2006

PubMed Abstract: Protein ubiquitination is a common form of post-translational modification that regulates a broad spectrum of protein substrates in diverse cellular pathways. Through a three-enzyme (E1-E2-E3) cascade, the attachment of ubiquitin to proteins is catalysed by the E3 ubiquitin ligase, which is best represented by the superfamily of the cullin-RING complexes. Conserved from yeast to human, the DDB1-CUL4-ROC1 complex is a recently identified cullin-RING ubiquitin ligase, which regulates DNA repair, DNA replication and transcription, and can also be subverted by pathogenic viruses to benefit viral infection. Lacking a canonical SKP1-like cullin adaptor and a defined substrate recruitment module, how the DDB1-CUL4-ROC1 E3 apparatus is assembled for ubiquitinating various substrates remains unclear. Here we present crystallographic analyses of the virally hijacked form of the human DDB1-CUL4A-ROC1 machinery, which show that DDB1 uses one beta-propeller domain for cullin scaffold binding and a variably attached separate double-beta-propeller fold for substrate presentation. Through tandem-affinity purification of human DDB1 and CUL4A complexes followed by mass spectrometry analysis, we then identify a novel family of WD40-repeat proteins, which directly bind to the double-propeller fold of DDB1 and serve as the substrate-recruiting module of the E3. Together, our structural and proteomic results reveal the structural mechanisms and molecular logic underlying the assembly and versatility of a new family of cullin-RING E3 complexes.

PubMed: 16964240
DOI: 10.1038/nature05175

Experimental method

X-RAY DIFFRACTION (3.1 Å)