IndraLab

Statements


29 | 42 10

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"The third DEP, PSMD7 (Rpn8), is part of the Rpn8-Rpn11 heterodimer with a function in removal of polyubiquitin tags before protein degradation in the proteasome 30 ."

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"A proteasomal subunit in close proximity to the Rpn8-Rpn11 heterodimer is PSMD13 (Rpn9), which showed a trend towards upregulation (fold change = 4.2; p = 0.07)."

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"A possible explanation for this finding is that SMK-24 may have bound effectively to the purified recombinant Rpn11/Rpn8 heterodimer, but not to endogenous Rpn11 in the greater structure of the 26S proteasome."

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"Proteasome 26S subunit, non-ATPase 7 (PSMD7, Rpn8, Mov34), an ATP-independent component of the 19S regulatory subunit, forms the heterodimers with PSMD14 as a functional complex which is extremely critical for degradation of ubiquitinated substrate with the proteasome [ xref ]."

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"PSMD7 interacts with PSMD14 to activate proteasome function to regulate ubiquitinated substrate degradation."

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"The Rpn11/Rpn8 heterodimer was expressed and purified as previously described ."

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"PSMD7 interacts with PSMD14 to activate proteasome function to regulate ubiquitinated substrate degradation."

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"The yeast RPN11/RPN8 complex, which is comparable to the human PSMD14/PSMD7 complex, has previously been reported to hydrolyse all isopeptide-linked diubiquitins ."

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"The RPN11/RPN8 complex is reported to process all linkages, however the catalytic efficiency for the processing of Lys11-linked diUb is two times higher as for Lys48-linked diUb and four times higher as for Lys63-linked diUb ."

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"Indeed, the minimal DUB-component complex of PSMD14 corresponds to the obligate PSMD14-PSMD7 heterodimers [ 18 , 26 ]."

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"Alternatively, it has been demonstrated that inactivation of PSMD14 in the context of the PSMD14-PSMD7 heterodimer is dependent on its RPN11's (PSMD14) Insert-1 (Ins-1) loop, which blocks the catalyti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The final Rpn8-Rpn11 heterodimer model is shown is Figure 3A and Figure S1C."

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"After transferring Zn ion to the Rpn11, we used both the Rpn11 monomer (Figure 2A) and the Rpn8-Rpn11 heterodimer (Figure 3A) structures for subsequent analysis.For the CSN5 monomer (Figure 2B), the recently solved crystal structure of CSN5 with CSN5i-3 (PDB_code: 5JOG) (Schlierf et al., 2016) was considered."

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"Therefore, it is now important to define whether this non-canonical function of PSMD14 on autophagy is either related to the free the heterodimer PSMD14-PSMD7, lid subcomplex or 19S RP ( Fig. 1 )."

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"This transition is likely facilitated by the distortion of Rpn11–Rpn5 and Rpn8–Rpn9 contact sites caused by interactions with the core and base subunits, and/or via displacement of the Rpn8/Rpn11 heterodimer by Rpn10 incorporation."

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"One path is initiated by dimerization of Rpn8 and Rpn11, which then recruits Rpn6 [52]."

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"This extension, coupled with repositioning of the Rpn8Rpn11 heterodimer described below [83], exposes key surfaces that contact the base, permitting their stable interaction."

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"Indeed, although the Rpn11/Rpn8 heterodimer has not been observed to accumulate appreciably in cells, substantial free lid has been observed [51], necessitating some regulatory mechanism to prevent spurious deubiquitination.Cryo-EM demonstrated that Rpn11 exists in an inhibited form in the isolated lid that explains these biochemical observations (Figure 6) [83]."

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"This dual mechanism of inhibition is also mediated in part via interactions between Rpn8 and Rpn9 that hold the Rpn8Rpn11 heterodimer downward against the palm of the hand-like lid subcomplex."

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"The starting structures of CSN5i-3 bound to the monomeric Rpn11 and Rpn8-Rpn11 heterodimer were generated by manual docking."

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"PSMD14 and Rpn11 forms a dimer with PSMD7 and Rpn8 and catalyzes deubiquitylation."

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"Thus, we investigated whether this was an unrealistic over binding, a protein-protein complex environment would be able to reproduce the selectivity.In the heterodimeric Rpn8-Rpn11 complex, CSN5i-3 binding in the pocket was not stable (Figure 7C), the distance to zinc increases continously and eventually the ligand lost coordination with Zn (Figure 7D and Table 1) which shows that the influence of Rpn8 on the capzimin bound Rpn11 is prominent."

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"LIE calculations (Table 2) revealed that CSN5i-3 binds moderately to the monomeric Rpn11 and very weakly to the Rpn8-Rpn11 heterodimer."

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"Binding of capzimin and CSN5i-3 to monomeric Rpn11 and Rpn8-Rpn11 heterodimer."

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"Both crystal structures of the yeast Rpn8-Rpn11 heterodimer (Pathare et al., 2014) and the cryo-EM structure of human 26S proteasome (Huang et al., 2016) show that the α2 helices of both proteins makes extensive contacts with each other.Molecular dynamics simulations refined the binding position of capzimin."

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"27 Å in Rpn11 monomer and Rpn8-Rpn11 heterodimer, respectively."

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"Capzimin showed almost similar binding affinity to monomeric Rpn11 as well as Rpn8-Rpn11 heterodimer (Table 2)."

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"In the Rpn8-Rpn11 heterodimer, capzimin showed a bidentate coordination with Zn and a stable H-bond with side chain of Thr129 (Figure S4B)."

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"However in the case of the Rpn8-Rpn11 heterodimer, CSN5i-3 showed only very weak interaction."

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"In the case of the Rpn8-Rpn11 heterodimer, LIE calculations showed only a very low binding energy of CSN5i-3 (Table 2) which is in agreement with the reported ligand binding selectivity."

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"Here we describe a method for the purification of the Rpn8/Rpn11 heterodimer and ubiquitin-GC-TAMRA, a model substrate that can be used to characterize the DUB activity of Rpn11 in isolation without the need of purifying 26S proteasomes."

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"A notable exception was the weaker interaction between the two non-ATPase lid subunits, GlRpn11 and GlRpn8, compared to the strong interaction between yeast orthologs Rpn11 and Rpn8."

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"Systematic evaluation of PSMD1-14 expression revealed significant upregulation (p<0.05) of PSMD1, PSMD2, PSMD3, PSMD4, PSMD7-PSMD14 transcripts in pancreatic tumor tissues compared with adjacent normal controls, with the notable exception of PSMD6 which demonstrated reduced mRNA expression ( xref )."

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"We propose that disruption of the PSMD7 and PSMD14 complex may block p53 degradation in the proteasome and therefore trigger cell cycle arrest, senescence and apoptosis in LUAD cells."

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"We propose that disruption of the PSMD7 and PSMD14 complex may block p53 degradation in the proteasome and therefore trigger cell cycle arrest, senescence and apoptosis in LUAD cells."

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"Disruption of PSMD14 and PSMD7 heterodimers may affect p53 degradation in the proteasome."

sparser
"Disruption of PSMD14 and PSMD7 heterodimers may affect p53 degradation in the proteasome."

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"Research on the proteasome holoenzyme revealed that PSMD14 and PSMD7 can form a dimer, which is locating directly above the central pore and leading the degraded substrate enter into the N‐terminal‐domain ring of the base ATPases xref ."

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"During the assembly of the lid, it has been detected that Rpn8/PSMD7 and Rpn11/PSMD14 form a heterodimer that exhibits PSMD14 activity [ 19 , 20 ]."

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"Research on the proteasome holoenzyme revealed that PSMD14 and PSMD7 can form a dimer, which is locating directly above the central pore and leading the degraded substrate enter into the N-terminal-domain ring of the base ATPases 13."

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"Alternatively, it has been demonstrated that inactivation of PSMD14 in the context of the PSMD14-PSMD7 heterodimer is dependent on its RPN11's (PSMD14) Insert-1 (Ins-1) loop, which blocks the catalyti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The Rpn8 and Rpn11 subunits, both of which harbor an Mpr1-Pad1 N-terminal (MPN)-domain, form a heterodimer and sits in the center of the palm, whereas the N-terminal α-solenoid domains of all PCI-cont[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Several deubiquitinases (DUBs), including PSMD7 and PSMD14 that form the minimal DUB‐competent complex in the proteasome, xref , xref are elevated in bortezomib‐treated iNs (Figure  xref )."

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"This Rpn11-Rpn8 heterodimer is thus the minimal DUB-competent complex of Rpn11."

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"Crystal structures and biochemical studies of the isolated Rpn11-Rpn8 heterodimer have previously revealed that Rpn11’s Insert-1 (Ins-1) loop blocks the catalytic groove but is also necessary for the [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"However, the mechanisms underlying the ATP dependence of Rpn11 ubiquitin cleavage and the potential coupling of substrate deubiquitination and degradation by the proteasome remain unclear.Here we pres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"This AAA+ motor-driven switch in Rpn11 thus allows a direct coupling of substrate deubiquitination and degradation at the proteasome and prevents Rpn11 from premature deubiquitination of substrates th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The ubiquitin-bound structure of Rpn11-Rpn8 thus provides important new insights into the mechanism of ubiquitin-substrate binding and deubiquitination during protein degradation by the proteasome.Bin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"REAGENT or RESOURCE SOURCE IDENTIFIER Bacterial and Virus Strains Escherichia coli Bl21-star (DE3) Thermo Fisher Scientific C601003 Escherichia coli Rosetta2 (DE3) pLysS Novagen 71403-3 Deposited Data[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Discrimination between single and double exponential fits was accomplished qualitatively using analysis of fit residuals and quantitatively using the F-test in the OriginPro model comparison tool.The [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"With regard to POH1, there is evidence that the isolated MPN heterodimer POH1-Rpn8 is more active in vitro than the 26S proteasome lid, which could lock Rpn11 in an inhibition state through Rpn5 [17]."

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"There is an interaction between PSMD7 and PSMD14 that activates proteasome function and modulates the degradation of ubiquitinated substrates."