IndraLab
Statements
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"Similarly, the peripherally associated proteasome DUBs Ubp6 and Uch37 are located adjacent to different ubiquitin receptors: Uch37 binds the proteasome through Rpn13, whereas the UBL of Ubp6 is tethered to Rpn1 at the T2 site that is distinct from the T1 ubiquitin binding site ( xref , xref , xref , xref )."
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"The structure of Calypso–ASX is reminiscent of the activated deubiquitinase complex observed for UCH-L5 bound to the Deubad domain of Rpn13 (Supplementary Fig. xref , left panel) (PDB codes: 4UEM and 4WLQ), rather than the inhibitory Deubad INO80G bound to the same UCH DUB (Supplementary Fig. xref , right panel) (PDB codes: 4UF5 and 4WLP) xref , xref ."
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"Usp14 (yeast UBP6) is associated with Rpn1 xref and Uch37 binds to the C-terminal domain of Rpn2-bound Rpn13; i.e., Uch37 associates with the base via Rpn13. xref , xref Intriguingly, deubiquitylation by Uch37 is activated by proteasome binding, which is also involved in the editing of polyubiquitin chains."
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"Our strategies for targets 98 and 99, RPN13-UCH-L5 binding, were based on the observation that RPN13 bound to the KEKE motif at the C-terminal end of UCH-L5. xref Through ZDOCK’s blocking feature we restricted binding to the C-terminus, and the bound structures showed that this assumption was correct."
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"In vitro binding of Uch37 with Rpn13 was shown to promote the hydrolysis of ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) and Uch37's reactivity with suicide inhibitors such as ubiquitin vinylsulfone (UbVS) and ubiquitin aldehyde (Ubal). xref Activation appeared to be regulated in part by the C-terminal domain of Uch37, xref as removal of the residues 238-329 provided enhanced hydrolase activity."
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"The region in Uch37 that interacts with hRpn13 is aggregation
prone xref xref xref and it is possible that the small reduction
of Uch37 immunoprecipitated with hRpn13 in RA190-treated cells is caused by
nonspecific interactions with this region when RA190 is adducted to the Uch37
catalytic domain."
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"As PSMD1 (scRpn2) encodes for the largest non-ATPase subunit of the 19S regulator lid of the 26S proteasome and this is involved in binding to the deubiquitinase UCH37 (scUCHL5) via the adapter protein ADRM1 (scRpn13), we hypothesized that knockout of PSMD1 may be disrupting the binding of UCH37 to the 26S proteasome, thereby inhibiting its deubiquitinase activity and leading to HIV-1 reactivation xref (Fig. xref )."