2vhf | pdb_00002vhf
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| 2vhf, resolution 2.800Å | |||||||||||||
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| Sites: | AC1, AC2, AC3 and AC4 | ||||||||||||
| Ligands: | ZN | ||||||||||||
| Activity: | Ubiquitin thiolesterase, with EC number 3.1.2.15 | ||||||||||||
| Related: | 1IXD, 1WHL, 1WHM
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
STRUCTURE OF THE CYLD USP DOMAIN
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. 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
Page seeded by OCA on Mon Mar 31 05:12:21 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Single protein
- Ubiquitin thiolesterase
- Ashworth, A.
- Barford, D.
- Hofmann, K.
- Komander, D.
- Lord, C J.
- Scheel, H.
- Swift, S.
- Alternative splicing
- Anti-oncogene
- B-box
- Cell cycle
- Cell signalling
- Cross-brace
- Cytokine signalling
- Cytoplasm
- Deubiquitinating enzyme
- Hydrolase
- Linkage specificity
- Lys63- linked
- Nf-kb
- Phosphorylation
- Protease
- Thiol protease
- Ubiquitin
- Ubl conjugation pathway
- Usp domain
- Zn-binding domain
