2VHF

Structure of the CYLD USP domain

Summary for 2VHF

• Entry DOI: 10.2210/pdb2vhf/pdb
• Related: 1IXD 1WHL 1WHM
• Descriptor: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE CYLD, ZINC ION (3 entities in total)
• Functional Keywords: cytokine signalling, linkage specificity, deubiquitinating enzyme, lys63- linked, anti-oncogene, thiol protease, cell signalling, phosphorylation, zn-binding domain, ubiquitin, cell cycle, usp domain, cross-brace, nf-kb, b-box, protease, hydrolase, cytoplasm, alternative splicing, ubl conjugation pathway
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q9NQC7
• Total number of polymer chains: 2
• Total formula weight: 86952.00

Authors

Komander, D.,Lord, C.J.,Scheel, H.,Swift, S.,Hofmann, K.,Ashworth, A.,Barford, D. (deposition date: 2007-11-21, release date: 2008-03-11, Last modification date: 2024-05-08)

Primary citation

Komander, D.,Lord, C.J.,Scheel, H.,Swift, S.,Hofmann, K.,Ashworth, A.,Barford, D.
The Structure of the Cyld Usp Domain Explains its Specificity for Lys63-Linked Polyubiquitin and Reveals a B-Box Module
Mol.Cell.Biol., 29:451-, 2008

PubMed Abstract: 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.

PubMed: 18313383
DOI: 10.1016/J.MOLCEL.2007.12.018

Experimental method

X-RAY DIFFRACTION (2.8 Å)