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COPS5 binds COPS6. 117 / 118
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"Molecular dynamics simulation studies further suggest that heterodimerization of CSN5 with CSN6 facilitates inhibitor binding by stabilizing an open ins-1 loop conformation [ 58 ]."
36041947
hprd
No evidence text available
12220626
hprd
No evidence text available
11285227
reach
"CSN5 and CSN6, which have an MPN (Mpr1 and Pad1 N-terminal) domain, form a dimer and are embedded at the core of the helical bundle."
29616013
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"The structure reaffirms the conserved activation mechanism of the deneddylation machinery, including conformational clamping of CRL2 by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer, and s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33271439
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"The above suggests that the MPN dimer (CSN5–CSN6 dimer) could be highly conserved."
33806190
hprd
No evidence text available
11337588
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"Structurally, CSN6 and CSN5 form a heterodimer through MPN domain and the dimer is topologically knotted to engage in Cullin deneddylation xref ."
25395170
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"MD simulations studies and binding energy analysis revealed that the selective binding of the inhibitors can be only explained by the consideration of larger heterodimeric complexes of Rpn11 (Rpn8-Rpn11) and CSN5 (CSN5-CSN6)."
30356695
sparser
"In the crystal structure of CSN5-CSN6 heterodimer, initial Ins-1 loop (98–109) conformation blocks the distal ubiquitin binding site which we also observed in cryo-EM structure of Rpn11."
30356695
sparser
"Rpn8-RPN11 and CSN5-CSN6 heterodimeric states are shown in Figure xref ."
30356695
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"Such a topological variation is accommodated by the differential pivotal angles of the CSN5-CSN6 dimer related to the rest of CSN."
41404609
sparser
"Binding of capzimin and CSN5i-3 to monomeric CSN5 and CSN5-CSN6 heterodimer."
30356695
sparser
"MD simulation of capzimin with monomeric CSN5 and CSN5-CSN6 heterodimer revealed that its binding to CSN5 is also influenced by the CSN6 (Figure xref )."
30356695
sparser
"In the CSN5-CSN6 heterodimer we observed that CSN5i-3 is stable (Figure xref ) and its conformation is very close to the conformation reported in the crystal structure (Figure xref )."
30356695
sparser
"However, in the CSN5-CSN6 heterodimer, CSN5i-3 forms stable H-bonds with both Thr154 and Asn158 (Figure xref and Figure xref )."
30356695
sparser
"For example, the main interactions at the interface in Rpn11-Rpn8 [24] and CSN5-CSN6 [25] heterodimers involve the residues from the two helices, and the α2-helix in AMSH-LP plays a role in substrate [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27240952
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"This CSN4 arm shift is accompanied by a coordinated movement of the CSN5-CSN6 heterodimer, ensuring the preservation of the essential interface between CSN4 and CSN6 Ins-2 (Supplementary Fig.  xref )."
41577659
sparser
"This may be the reason behind lower flexibility of Ins-1 loop in the monomeric CSN5 compared to the CSN6 bound CSN5."
30356695
biogrid
No evidence text available
33961781
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"However, in the CSN5-CSN6 heterodimer, capzimin displayed a monodentate coordination with Zn 2+ and only low occupancy H-bonds with side chains of Met78, Arg106, and Asn158 (Figure xref )."
30356695
sparser
"Since the N-terminal region of ODR4 is predicted to have an MPN domain, it is tempting to suggest that the interactions seen between the MPN domains in the Rpn11-Rpn8 [24] and CSN5-CSN6 [25] multi-pro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27240952
sparser
"To further characterize the inhibitor, we used biolayer interferometry (BLI) and measured the affinity of CSN5i-3 to a purified CSN5-CSN6 heterodimer."
41404609
sparser
"Considering the Rpn8-Rpn11 and CSN5-CSN6 heterodimers, we found that residues in the distal ubiquitin site are responsible for selectivity and must be taken into consideration for the design of selective inhibitors of CSN5 and Rpn11 in future studies."
30356695
sparser
"Strikingly, the dissociation constant, K D , of the inhibitor-CSN5-CSN6 interaction was determined to be ~4 μM ( xref ), which differs from the originally reported potency of CSN5i-3 (~5.8 nM) by three orders of magnitude xref ."
41404609
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"Alternatively, based on recent finding on the structure of eight-unit COP9 complex XREF_BIBR, it is possible to modulate COPS5 activity by tackling the interactions between COP9 subunits, particularly the interaction between COPS5 and COPS6 and CSN6 subunits that is crucial for maintaining the isopeptidase activity."
27375289
biogrid
No evidence text available
27173435
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No evidence text available
21145461
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"The cap sits at the top of the box and consists of a CSN5–CSN6 heterodimer ( xref ) ( xref )."
28271482
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"Taken together, COPS5 and COPS6 were associated with the survival of the HNSCC cells and could be detected in tumor samples using IHC."
34630710
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"Structural data provide evidence for coordinated domain changes of CSN2, CSN4, and CSN7 and the CSN5-CSN6 heterodimer induced by neddylated CRL4A converting CSN5 into its active conformation [37]."
32708147
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"In analogy to the CSN5-CSN6 heterodimer, RPN11 partners with another MPN domain protein, RPN8, possessing an inactive JAMM domain."
32708147
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"Sitting atop…is the CSN5–CSN6 tomato….” [ xref ])."
31195722
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"In plants, the COP9 signalosome consists of nine subunits, with its structural core formed by CSN5 and CSN6, both harboring the Mpr1-Pad1 N-terminal (MPN) domain."
41095159
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"Interaction of the complex with a NEDDylated CRL leads to a series of conformational change events in Csn2, Csn4 and Csn7, triggering rearrangements in the Csn5–Csn6 dimer, resulting in Csn5 activation by priming the Csn5 JAMM/MPN + motif for deNEDDylation [ xref , xref ]."
33099217
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"The core of the complex is formed by CSN5 and CSN6, while CSN1–CSN4, CSN7, and CSN8 assemble into a peripheral ring ( xref )."
41095159
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"Structural and Biochemical Characterization of the Cop9 Signalosome CSN5 and CSN6 Heterodimer."
25144743
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"The CSN complex consists of six proteasome lid–CSN–initiation factor 3 (PCI) domain-containing subunits (CSN1-4, CSN7, CSN8), which form a horseshoe-shaped scaffold, and an MPN domain heterodimer (CSN5-CSN6) harbouring the catalytic site xref ."
41577659
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"The structure of the CSN5-CSN6 heterodimer (Figure S3A) was extracted from the crystal structure of human COP9 signalasome (PDB_code: 4D10) (Lingaraju et al., 2014) C-terminal regions of CSN5 (258–333) and CSN6 (215–316) were also deleted since they are not involved in catalysis and heterodimer formation can take place without them."
30356695
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"The processed CSN5-CSN6 heterodimer is shown in Figure 3B and Figure S3C."
30356695
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"Structural data provide evidence for coordinated domain changes of CSN2, CSN4, and CSN7 and the CSN5-CSN6 heterodimer induced by neddylated CRL4A converting CSN5 into its active conformation [ xref ]."
32708147
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"Upon CRL–CSN engagement, the CRLs dock between CSN2 and CSN4, weakening the CSN4–CSN6 interface and releasing the CSN5–CSN6 MPN dimer."
41095159
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"In the crystal structure of CSN5-CSN6 heterodimer, initial Ins-1 loop (98–109) conformation blocks the distal ubiquitin binding site which we also observed in cryo-EM structure of Rpn11."
30356695
sparser
"In analogy to the CSN5-CSN6 heterodimer, RPN11 partners with another MPN domain protein, RPN8, possessing an inactive JAMM domain."
32708147
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"These data suggests a hierarchy in the catalytic activity over the enzymatic system and the substrate type, with the inactive CSN5 DeltaC, WT form, CSN5 DeltaC, R106T that has basal activity, the MPN heterodimer alone that has robust isopeptidase activity on non physiological substrates and the CSN5 and CSN6 heterodimer in the context of CSN that recapitulates strong activity on both non physiological and physiological substrates."
25144743
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"To test this idea, we first assessed the potency of CSN5i-3 in inhibiting the intrinsic catalytic activity of the CSN5-CSN6 heterodimer towards NEDD8-rhodamine."
41404609
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"Binding of capzimin and CSN5i-3 to monomeric CSN5 and CSN5-CSN6 heterodimer."
30356695
sparser
"Such a high potency is in stark contrast to its μM affinity of binding free CSN5-CSN6 and is close to its potency in inhibiting N8~CRL1 deneddylation by the intact CSN ( xref , xref , xref )."
41404609
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"After particle selection through 2D and 3D classification, we obtained an initial map at 3.2 Å. However, the CSN5-CSN6 and NEDD8-WHB ( N8 CUL1 WHB ) regions were poorly resolved, likely due to conformational heterogeneity."
41577659
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"First, the catalytic activity efficiency can be achieved by an increase of affinity for Nedd8 observed either in the CSN5 and CSN6 complex or by the conformational relaxation of the Ins-1 segment."
25144743
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"MD simulation of capzimin with monomeric CSN5 and CSN5-CSN6 heterodimer revealed that its binding to CSN5 is also influenced by the CSN6 (Figure 10)."
30356695
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"The catalytic subunit CSN5 forms a subcomplex with CSN6 and CNS4."
26073511
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"In the CSN5-CSN6 heterodimer we observed that CSN5i-3 is stable (Figure 12C) and its conformation is very close to the conformation reported in the crystal structure (Figure S6)."
30356695
reach
"However, in the CSN5-CSN6 heterodimer, CSN5i-3 forms stable H-bonds with both Thr154 and Asn158 (Figure S5D and Figure 13B)."
30356695
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"As shown in Figure 2C, Flag-Csn6 fusion proteins could be identified in proteins copurified with GFP-Csn5, further confirming the interaction between Csn5 and Csn6."
37168110
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"CSN is assembled into the previously described horseshoe-shaped ring xref , formed by association of the winged-helix (WH) subdomains from the six proteasome lid–CSN–initiation factor 3 (PCI ring) containing subunits (CSN1-4 and CSN7-8), along with the globular CSN5-CSN6 heterodimer."
41577659
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"This may be the reason behind lower flexibility of Ins-1 loop in the monomeric CSN5 compared to the CSN6 bound CSN5."
30356695
sparser
"We generated a single mask incorporating both NEDD8 positions for 3D local classification in RELION-4.0, which resulted in two major conformations with well-resolved but distinct CSN5-CSN6 and N8 CUL1 WHB regions."
41577659
reach
"However, in the CSN5-CSN6 heterodimer, capzimin displayed a monodentate coordination with Zn and only low occupancy H-bonds with side chains of Met78, Arg106, and Asn158 (Figure S5B)."
30356695
sparser
"The MPN domains of CSN5 and CSN6 form a stable heterodimer."
25144743
biogrid
No evidence text available
19141280
sparser
"Previous structural studies of the CSN suggested that CSN5 and CSN6 interact xref , xref ."
25144743
sparser
"The association of the 1–257 and 31–211 domains of CSN5 and CSN6, amenable to soluble bacterial expression, referred to as CSN5 ΔC and CSN6 Δ , respectively ( xref , xref ) was probed by ITC experiments."
25144743
sparser
"For instance, in plant cells, isoforms have been identified for the MPN‐domain subunits CSN5 (CSN5A and CSN5B) and CSN6 (CSN6A and CSN6B) which form four distinct CSN variants."
27833851
sparser
"As shown in xref , Flag-Csn6 fusion proteins could be identified in proteins copurified with GFP-Csn5, further confirming the interaction between Csn5 and Csn6."
37168110
sparser
"Each of the above multiprotein complexes contains a single heterodimer of MPN proteins, usually with one catalytically active and one inactive monomer (POH1-Rpn8 in the proteasome, CSN5-CSN6 in the signalosome and BRCC36-Abraxas in the RAP80 complex)."
35501388
sparser
"This analysis could strengthen the view that CSN5 ΔC and CSN6 ΔC interact through an architecture reminiscent of the Rpn11 ΔC /Rpn8 ΔC complex."
25144743
sparser
"Both complexes contain an MPN dimer (CSN5-CSN6 in the COP9 signalosome and POH1-Rpn8 in the proteasome lid) and six PCI-domain proteins."
35501388
sparser
"Therefore, to characterise further this complex, we probed the association of CSN5 ΔC and CSN6 ΔC by NMR to help define the regions responsible for the interaction."
25144743
sparser
"It is noteworthy that, although the interaction between CSN5 ΔC and CSN6 ΔC was impaired by the H44A or to a stronger extent by the V115A substitution, the effect of these variants remains modest (2 to 5-fold)."
25144743
sparser
"However, the Y2H results showed that Csn5 only directly interacted with Csn6 but not the other five Csn subunits ( xref ), implying that Csn5 may associate but not directly interact with others."
37168110
sparser
"Exploiting the above detailed finding that CSN5 ΔC and Nedd8 interaction proceeds through similar surfaces to that of AMSH-LP-distal ubiquitin's ( xref , xref ), a complex composed of CSN5 ΔC displaying an AMSH-LP-like Ins-1 conformation and of Nedd8 was assembled and used to probe the association of CSN5 ΔC and CSN6 ΔC ."
25144743
sparser
"In addition to the Csn5-Csn6 interaction, nine other interaction pairs were detected in this study, including Csn1-Csn2, Csn1-Csn3, Csn1-Csn4, Csn2-Csn3, Csn3-Csn4, Csn3-Csn6, Csn4-Csn6, Csn4-Csn7, and Csn6-Csn7 ( xref )."
37168110
sparser
"Because CSN5i-3 physically occludes the CSN5 active site and does not directly contact the iso-peptide bond formed between NEDD8 and CUL1 Lys-720, we replaced NEDD8~rhodamine with native NEDD8 and measured its affinity toward the CSN5-CSN6 heterodimer in the presence and absence of CSN5i-3."
41404609
sparser
"We can conclude that CSN6 51–187 dimeric interactions may provide the basis for CSN5 homodimer or CSN5-CSN6 heterodimer [28–30] ."
22575649
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"Several interactions, including Csn1-Csn2, Csn1-Csn4, Csn4-Csn7, Csn4-Csn6, and Csn5-Csn6, were all demonstrated in these organisms ( xref ; xref )."
37168110
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"In our CSN6 homodimer structure, alpha1 and alpha2 from one monomer interact with alpha2 and alpha1 from another monomer, respectively, while in the CSN5 and CSN6 heterodimer, alpha1 and alpha2 helice[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25242525
sparser
"Interestingly, while the interaction between NEDD8 and CSN5-CSN6 was barely detectable by BLI, they acquired a high affinity of ~930 nM when CSN5i-3 was present at a saturating concentration ( xref )."
41404609
sparser
"The key structural rearrangements include: (i) the presence of a neddylated SCF triggers the convergence of the N-terminal helical arms of CSN2 and CSN4 (hereafter CSN2 arm and CSN4 arm respectively), clamping CUL1 CTD and RBX1 RING , (ii) the flexible CUL1 WHB is repositioned against the stabilised RBX1 RING , aligning NEDD8 at the CSN active site and (iii) concurrent disruption of the CSN4-CSN6 interface enables flexibility and remodelling of the CSN5-CSN6 MPN domains, bringing the CSN5 active site closer to NEDD8 (Fig.  xref )."
41577659
biogrid
No evidence text available
31950832
sparser
"Another CSN-associated DUB is the signal transducing adapter molecule (STAM) binding protein like 1 (STAMBPL1), which is a ubiquitous metalloprotease DUB that copurifies with the CSN and interacts wit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36041947
biogrid
No evidence text available
19295130
reach
"Moreover, in the CSN5 and CSN6 heterodimer, alpha4 helix of CSN6, a C-terminal extension of the MPN domain, interacts with alpha6 helix of CSN5."
25242525
sparser
"Then, with the binding of neddylated SCF Skp2/Cks1 , topological conformation change occurs in the CSN5-CSN6 dimer, resulting in CSN5 activation."
35883466
biogrid
No evidence text available
25144743
biogrid
No evidence text available
25144743
biogrid
No evidence text available
21145461
biogrid
No evidence text available
32034103
biogrid
No evidence text available
32034103
sparser
"Unlike the N-terminal, the extended C-terminal helix of each CSN1–CSN8 subunit forms a helical bundle while the CSN5 and CSN6 heterodimers with MPN domains adopt globular conformations just above the helical bundle [ xref , xref ]."
35883466
sparser
"As a result, the CSN5-CSN6 dimer undergoes conformational rearrangement to facilitate movement toward the directed CRL4A DDB2 [ xref ]."
35883466
biogrid
No evidence text available
26344197
biogrid
No evidence text available
26186194
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No evidence text available
21625211
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No evidence text available
28514442
sparser
"Structurally, CSN6 and CSN5 form a heterodimer through MPN domain, and the dimer is topologically knotted to engage in Cullin deneddylation ( xref )."
26267535
biogrid
No evidence text available
19615732
biogrid
No evidence text available
19615732
biogrid
No evidence text available
19295130
reach
"We can conclude that CSN6 51–187 dimeric interactions may provide the basis for CSN5 homodimer or CSN5-CSN6 heterodimer [28–30] ."
22575649
biogrid
No evidence text available
22863883
sparser
"This increased flexibility, in turn, triggers a substantial rotation of the CSN5-CSN6 MPN heterodimer (Supplementary Fig.  xref ), repositioning CSN5 and NEDD8 closer to each other."
41577659
biogrid
No evidence text available
21145461
sparser
"While in the absence of the substrate (neddylated cullin) CSN5 is in an inactive conformation, substrate binding leads to a dramatic domain motion of CSN4, which moves the CSN5–CSN6 dimer away from th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26096786
sparser
"The helical bundle closely associated with the CSN5–CSN6 dimer [17] is perhaps involved in conformational changes regulating CSN activity in response to phosphorylation."
26096786
reach
"The catalytic subunit CSN5 forms a subcomplex with CSN6 and CNS4."
26073511
sparser
"In the presence of CRL4A, conformational changes in CSN2, CSN4, and CSN7 affect the CSN5-CSN6 dimer and activate CSN5."
39600336
sparser
"The maps vary in the density observed for CUL1 WHB , RBX1 RING and the CSN5-CSN6 heterodimer, indicating conformational flexibility within the system."
41577659
sparser
"The resulting structural model confirms the previously described global architectural changes in CSN upon binding N8~CRLs, which are highlighted by the pivotal movement of the CSN5-CSN6 dimer induced by the association of CUL1-CTD-RBX1 with CSN2 and CSN4."
41404609
sparser
"Upon engaging N8~CRL1, the rotation movement of the CSN5-CSN6 dimer pivots the CSN5 Ins-2 loop away from the helical bundle."
41404609
biogrid
No evidence text available
35831314
sparser
"Yet, with CSN5 released from NEDD8, flexibility is introduced, resulting in insufficient CSN5-CSN6 density for model building."
41577659
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"The MPN domains of the CSN5 and CSN6 heterodimer rest on the helical bundle while their carboxy terminal helical tails are inserted into the helical bundle."
26437438
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18850735
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22939629
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"Analogous with dissociation-state-2, CSN4 arm is disengaged from CUL1 CTD (Supplementary Fig.  xref ), and CSN5-CSN6 are held in their autoinhibited positions by CSN4 (Supplementary Fig.  xref )."
41577659
reach
"38 Also the MPN domain is involved in heterodimerization between CSN6 and CSN5 to regulate Cullin neddylation."
33101846