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2vhf
From Proteopedia
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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 with as ligand. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Known structural/functional Sites: , , and . 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 Fri Mar 14 09:35:44 2008
Categories: Homo sapiens | Single protein | Ubiquitin thiolesterase | Ashworth, A. | Barford, D. | Hofmann, K. | Komander, D. | Lord, C J. | Scheel, H. | Swift, S. | ZN | 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
