2hye
From Proteopedia
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Crystal Structure of the DDB1-Cul4A-Rbx1-SV5V Complex
Overview
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.
About this Structure
2HYE is a Protein complex structure of sequences from Homo sapiens and Simian virus 40 with as ligand. Full crystallographic information is available from OCA.
Reference
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery., Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N, Nature. 2006 Oct 5;443(7111):590-3. PMID:16964240
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