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PDBsum entry 3wxf
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Hydrolase/protein binding
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PDB id
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3wxf
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References listed in PDB file
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Key reference
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Title
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Structures of cyld usp with met1- Or lys63-Linked diubiquitin reveal mechanisms for dual specificity.
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Authors
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Y.Sato,
E.Goto,
Y.Shibata,
Y.Kubota,
A.Yamagata,
S.Goto-Ito,
K.Kubota,
J.Inoue,
M.Takekawa,
F.Tokunaga,
S.Fukai.
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Ref.
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Nat Struct Mol Biol, 2015,
22,
222-229.
[DOI no: ]
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PubMed id
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Abstract
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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.
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