3WXF

Crystal structure of CYLD USP domain (C596S E674Q) in complex with Met1-linked diubiquitin

Summary for 3WXF

• Entry DOI: 10.2210/pdb3wxf/pdb
• Related: 3WXE 3WXG
• Descriptor: Uncharacterized protein, Ubiquitin, SULFATE ION, ... (4 entities in total)
• Functional Keywords: ubiquitin protease, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Danio rerio (zebra fish); More
• Total number of polymer chains: 4
• Total formula weight: 105675.59

Authors

Sato, Y.,Fukai, S. (deposition date: 2014-07-30, release date: 2015-02-11, Last modification date: 2023-11-08)

Primary citation

Sato, Y.,Goto, E.,Shibata, Y.,Kubota, Y.,Yamagata, A.,Goto-Ito, S.,Kubota, K.,Inoue, J.,Takekawa, M.,Tokunaga, F.,Fukai, S.
Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity.
Nat.Struct.Mol.Biol., 22:222-229, 2015

PubMed Abstract: The tumor suppressor CYLD belongs to a ubiquitin (Ub)-specific protease (USP) family and specifically cleaves Met1- and Lys63-linked polyubiquitin chains to suppress inflammatory signaling pathways. Here, we report crystal structures representing the catalytic states of zebrafish CYLD for Met1- and Lys63-linked Ub chains and two distinct precatalytic states for Met1-linked chains. In both catalytic states, the distal Ub is bound to CYLD in a similar manner, and the scissile bond is located close to the catalytic residue, whereas the proximal Ub is bound in a manner specific to Met1- or Lys63-linked chains. Further structure-based mutagenesis experiments support the mechanism by which CYLD specifically cleaves both Met1- and Lys63-linked chains and provide insight into tumor-associated mutations of CYLD. This study provides new structural insight into the mechanisms by which USP family deubiquitinating enzymes recognize and cleave Ub chains with specific linkage types.

PubMed: 25686088
DOI: 10.1038/nsmb.2970

Experimental method

X-RAY DIFFRACTION (2.3 Å)