2hye
From Proteopedia
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| , resolution 3.1Å | |||||||
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| Ligands: | |||||||
| Gene: | DDB1 (Homo sapiens), P/V (Simian virus 5), CUL4A (Homo sapiens), RBX1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the DDB1-Cul4A-Rbx1-SV5V Complex
Contents |
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.
Disease
Known disease associated with this structure: Xeroderma pigmentosum, group E, subtype 2 OMIM:[600045]
About this Structure
2HYE is a Protein complex structure of sequences from Homo sapiens and Simian virus 5. 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
Page seeded by OCA on Mon Mar 31 03:37:10 2008
