IndraLab

Statements

WDR20 binds USP12. 30 / 31
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"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."
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"Consistent with our results on USP1, activation of USP12-WDR20 by UAF1 is achieved mainly through an 20-fold increase of k cat with little change in K M , suggesting that substrate affinity of USP12 is not altered by UAF1 ( Figures 6A and S5A-S5D) ."
27373336
biogrid
No evidence text available
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No evidence text available
21183687
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No evidence text available
26811477
sparser
"In the two UAF1-USP12 complex structures, UAF1 binding appears to induce BL1 destabilization via a chain of conformational changes, whereas the WDR20-USP12 interaction seems to overwrite the allosteric effect of UAF1 by re-stabilizing the loop."
27373336
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"Results confirmed the interaction between endogenous Usp12, Uaf-1 and WDR20 in PC cells."
26462181
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"Adjacent to the major USP12-WDR20 interface, the tip of USP12 BL3, which is otherwise disordered in both free and UAF1-bound forms of the enzyme, adopts a stable structure by making van der Waal contacts with WDR20."
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"Binding of WDR20 to the UAF1-USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub-bound USP46."
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"The k cat and K M values are presented as means ± SD (n = 3), and the K D values were obtained through steady-state analysis (see Supplemental Experimental Procedures for technical discussion). (B) Time course of USP12 modification by the suicidal Ub-VME substrate in the absence or presence of UAF1 and WDR20. (C) Time course of LRGG-AMC (top) in contrast to Ub-AMC (bottom) hydrolysis by USP12 (green), UAF1-USP12 (orange), and USP12-WDR20 (red)."
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"WDR20 interacts with the USP12 Palm domain, and it is paralleled with the WD40 repeat domain of UAF1 ( xref E)."
33498168
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"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [71,76]."
32512887
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"The second UAF1 binding site has low affinity and partially overlaps the WDR20-USP12 binding interface, thus the binding of WDR20 to USP12/UAF1 may prevent the second UAF1 molecule from binding to USP12, so it may have a regulatory effect [ xref ]."
33498168
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"As both Uaf-1 and WDR20 interact with Usp12 we hypothesised that Uaf-1 and WDR20 would also be found in a complex with AR."
26462181
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"Usp12, Uaf-1 and WDR20 form a complex acting within a positive feedback loop in PC cells."
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biogrid
No evidence text available
19615732
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"It is possible that binding of PHLPP or PHLPPL to Uaf-1 requires a conformational change that is facilitated by Uaf-1 becoming part of the WDR20 and Usp12 complex."
25216524
biogrid
No evidence text available
19615732
sparser
"In the two UAF1-USP12 complex structures, UAF1 binding appears to induce BL1 destabilization via a chain of conformational changes, whereas the WDR20-USP12 interaction seems to overwrite the allosteric effect of UAF1 by (D and E) Rates of Ub-AMC hydrolysis by wild-type (WT) and mutant USP12 in the presence of UAF1 (D) or WDR20 (E)."
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"The partial overlap of the binding interfaces and the high affinity of WDR20 suggests that WDR20 binding to USP12 and UAF1 can either prevent binding of the second UAF1 molecule or it can actively compete out UAF1 if it is bound to the USP12 and UAF1 complex."
27650958
sparser
"The predominant USP12-WDR20 interface also involves major structural elements that are topologically connected to UAF1 binding in the UAF1-USP12 structures."
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No evidence text available
26462181
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No evidence text available
26462181
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No evidence text available
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"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center."
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"Allosteric Activation of Ubiquitin-Specific Proteases by b-Propeller Proteins UAF1 and WDR20 Molecular Cell Article Allosteric Activation of Ubiquitin-Specific Proteases by b-Propeller Proteins UAF1 and WDR20.Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20Ubiquitin-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 b-propeller proteins, UAF1 and WDR20."
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"The WDR20-USP12 interface is centered on a row of three hydrophobic WDR20 residues, W306, F262, and Y261, which are further supported by their surrounding polar amino acid side chains and backbone groups."
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"Binding of WDR20 to the UAF1 and USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub bound USP46."
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"This model is inferred from a combination of structures of USP46 bound to WDR48 and ubiquitin (Yin et al., 2015) and USP12 bound to WDR48 and WDR20 (Li et al., 2016)."
29302259
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"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
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