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PDBsum entry 5k1b
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Protein binding/hydrolase
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PDB id
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5k1b
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References listed in PDB file
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Key reference
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Title
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Allosteric activation of ubiquitin-Specific proteases by β-Propeller proteins uaf1 and wdr20.
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Authors
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H.Li,
K.S.Lim,
H.Kim,
T.R.Hinds,
U.Jo,
H.Mao,
C.E.Weller,
J.Sun,
C.Chatterjee,
A.D.D'Andrea,
N.Zheng.
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Ref.
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Mol Cell, 2016,
63,
249-260.
[DOI no: ]
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PubMed id
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Abstract
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Ubiquitin-specific proteases (USPs) constitute the largest family of
deubiquitinating enzymes, whose catalytic competency is often modulated by their
binding partners through unknown mechanisms. Here we report on a series of
crystallographic and biochemical analyses of an evolutionarily conserved
deubiquitinase, USP12, which is activated by two β-propeller proteins, UAF1 and
WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two
distinct sites far from its catalytic center. Without increasing the substrate
affinity of USP12, the two β-propeller proteins potentiate the enzyme through
different allosteric mechanisms. UAF1 docks at the distal end of the USP12
Fingers domain and induces a cascade of structural changes that reach a critical
ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20
anchors at the base of this loop and remotely modulates the catalytic center of
the enzyme. Our results provide a mechanistic example for allosteric activation
of USPs by their regulatory partners.
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