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PDBsum entry 5jtj
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References listed in PDB file
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Key reference
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Title
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Molecular understanding of usp7 substrate recognition and c-Terminal activation.
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Authors
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L.Rougé,
T.W.Bainbridge,
M.Kwok,
R.Tong,
P.Di lello,
I.E.Wertz,
T.Maurer,
J.A.Ernst,
J.Murray.
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Ref.
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Structure, 2016,
24,
1335-1345.
[DOI no: ]
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PubMed id
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Abstract
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The deubiquitinating enzyme USP7 has a pivotal role in regulating the stability
of proteins involved in fundamental cellular processes of normal biology and
disease. Despite the importance of USP7, the mechanisms underlying substrate
recognition and catalytic activation are poorly understood. Here we present
structural, biochemical, and biophysical analyses elucidating the molecular
mechanism by which the C-terminal 19 amino acids of USP7 (residues 1084-1102)
enhance the ubiquitin cleavage activity of the deubiquitinase (DUB) domain. Our
data demonstrate that the C-terminal peptide binds the activation cleft in the
catalytic domain and stabilizes the catalytically competent conformation of
USP7. Additional structures of longer fragments of USP7, as well as solution
studies, provide insight into full-length USP7, the role of the UBL domains, and
demonstrate that both substrate recognition and deubiquitinase activity are
highly regulated by the catalytic and noncatalytic domains of USP7, a feature
that could be essential for the proper function of multi-domain DUBs.
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