2vhf | pdb_00002vhf

STRUCTURE OF THE CYLD USP DOMAIN

File:2vhf.jpg

spinqualitylabelsall models 2vhf, resolution 2.800Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Overview

The tumor suppressor CYLD antagonizes NF-kappaB and JNK signaling by disassembly of Lys63-linked ubiquitin chains synthesized in response to cytokine stimulation. Here we describe the crystal structure of the CYLD USP domain, revealing a distinctive architecture that provides molecular insights into its specificity toward Lys63-linked polyubiquitin. We identify regions of the USP domain responsible for this specificity and demonstrate endodeubiquitinase activity toward such chains. Pathogenic truncations of the CYLD C terminus, associated with the hypertrophic skin tumor cylindromatosis, disrupt the USP domain, accounting for loss of CYLD catalytic activity. A small zinc-binding B box domain, similar in structure to other crossbrace Zn-binding folds-including the RING domain found in E3 ubiquitin ligases-is inserted within the globular core of the USP domain. Biochemical and functional characterization of the B box suggests a role as a protein-interaction module that contributes to determining the subcellular localization of CYLD.

About this Structure

2VHF is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Known structural/functional Sites: AC1, AC2, AC3 and AC4. Full crystallographic information is available from OCA.

Reference

The Structure of the CYLD USP Domain Explains Its Specificity for Lys63-Linked Polyubiquitin and Reveals a B Box Module., Komander D, Lord CJ, Scheel H, Swift S, Hofmann K, Ashworth A, Barford D, Mol Cell. 2008 Feb 29;29(4):451-64. PMID:18313383

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