2hye

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spinqualitylabelsall models 2hye, resolution 3.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 40 with ZN 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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