IndraLab

Statements

UAF1 activates USP12. 10 / 10
| 10
eidos
"Based on our results , we propose a tenable model for USP12 activation by UAF1 and WDR20 ( Figure 7 ) ."
27373336
eidos
"First , our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity ."
27373336
eidos
"With a mutation introduced to the BL1 residue F262 , USP12 could no longer be activated by UAF1 but retained full WDR20-stimulated activity ( Figures 6D and 6E ) ."
27373336
eidos
"To gain deeper mechanistic insights into USP12 activation by UAF1 and WDR20 , we first determined the steady-state kinetics of substrate hydrolysis by USP12 in different forms ."
27373336
eidos
"To delineate the mechanism by which UAF1 activates USP12 , we next determined the crystal structure of USP12 in a complex with full-length human UAF1 in the F222 space group at 3 ."
27373336
eidos
"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 WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
27373336
eidos
"Activation of USP12 by UAF1 requires structural fine-tuning at the junction of the Ub globular domain and it tail through BL1 , whereas WDR20 acts independently of this site and directly affects the catalytic cleft ."
27373336
eidos
"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways ."
27373336
eidos
"UAF1 activates USP12 by binding to the tip of its Fingers domain and transmitting a long-range allosteric signal to BL1 ."
27373336
eidos
"Nevertheless , the free USP12 structure alone is insufficient to link these predicted changes to USP12 activation by UAF1 or WDR20 ."
27373336