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PDBsum entry 5cvl
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Protein binding
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PDB id
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5cvl
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References listed in PDB file
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Key reference
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Title
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Structural insights into wd-Repeat 48 activation of ubiquitin-Specific protease 46.
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Authors
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J.Yin,
A.J.Schoeffler,
K.Wickliffe,
K.Newton,
M.A.Starovasnik,
E.C.Dueber,
S.F.Harris.
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Ref.
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Structure, 2015,
23,
2043-2054.
[DOI no: ]
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PubMed id
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Abstract
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Protein ubiquitination patterns are an important component of cellular
signaling. The WD-repeat protein WDR48 (USP1-associated factor UAF-1) stimulates
activity of ubiquitin-specific proteases USP1, USP12, and USP46. To understand
how WDR48 exerts its effect on the USP scaffold, we determined structures of
the ternary WDR48:USP46:ubiquitin complex. WDR48 interacts with the USP46
fingers subdomain via a relatively small, highly polar surface on the top center
of the WDR48 β propeller. In addition, WDR48 has a novel ancillary domain and a
C-terminal SUMO-like domain encircling the USP46-bound ubiquitin. Mutation of
residues involved in the WDR48:USP46 interaction abrogated both binding and
deubiquitinase activity of the complex. An analogous mutation in USP1 similarly
blocked WDR48-dependent activation. Our data suggest a possible mechanism of
deubiquitinase stimulation via stabilization and prolonged residence time of
substrate. The unprecedented mode of interaction between the USP fingers domain
and the WD-repeat β propeller serves as a prototypical example for this family
of deubiquitinases.
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