IndraLab

Statements


18 3 | 21 28

sparser
"Binding of capzimin and CSN5i-3 to monomeric CSN5 and CSN5-CSN6 heterodimer."

No evidence text available

sparser
"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 Csn5Csn6 dimer, resulting in Csn5 activation by priming the Csn5 JAMM/MPN + motif for deNEDDylation [ xref , xref ]."

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."

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."

reach
"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."

sparser
"This may be the reason behind lower flexibility of Ins-1 loop in the monomeric CSN5 compared to the CSN6 bound CSN5."

sparser
"Structurally, CSN6 and CSN5 form a heterodimer through MPN domain and the dimer is topologically knotted to engage in Cullin deneddylation xref ."

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."

reach
"Structural and Biochemical Characterization of the Cop9 Signalosome CSN5 and CSN6 Heterodimer."

reach
"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]."

No evidence text available

reach
"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)."

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."

No evidence text available

sparser
"Interestingly, STAMBPL1 has a direct interaction with the constitutive photomorphogenic 9 (COP9 or CSN) signalosome subunits CSN5 and CSN6."

reach
"This may be the reason behind lower flexibility of Ins-1 loop in the monomeric CSN5 compared to the CSN6 bound CSN5."

No evidence text available

reach
"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."

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."

No evidence text available

sparser
"The above suggests that the MPN dimer (CSN5CSN6 dimer) could be highly conserved."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"Structurally, CSN6 and CSN5 form a heterodimer through MPN domain, and the dimer is topologically knotted to engage in Cullin deneddylation ()."

reach
"Binding of capzimin and CSN5i-3 to monomeric CSN5 and CSN5-CSN6 heterodimer."

No evidence text available

No evidence text available

sparser
"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)."

sparser
"Previous structural studies of the CSN suggested that CSN5 and CSN6 interact xref , xref ."

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 )."

sparser
"The cap sits at the top of the box and consists of a CSN5CSN6 heterodimer ( xref ) ( xref )."

No evidence text available

No evidence text available

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."

reach
"In analogy to the CSN5-CSN6 heterodimer, RPN11 partners with another MPN domain protein, RPN8, possessing an inactive JAMM domain."

No evidence text available

reach
"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]"

No evidence text available

sparser
"In analogy to the CSN5-CSN6 heterodimer, RPN11 partners with another MPN domain protein, RPN8, possessing an inactive JAMM domain."

reach
"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."

No evidence text available

reach
"The processed CSN5-CSN6 heterodimer is shown in Figure 3B and Figure S3C."

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 ."

sparser
"Rpn8-RPN11 and CSN5-CSN6 heterodimeric states are shown in Figure xref ."

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 )."

reach
"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)."

No evidence text available

reach
"These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2 and CSN4, release of the catalytic CSN5 and CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery."

No evidence text available

sparser
"However, in the CSN5-CSN6 heterodimer, CSN5i-3 forms stable H-bonds with both Thr154 and Asn158 (Figure xref and Figure xref )."

sparser
"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 ]."

sparser
"The MPN domains of CSN5 and CSN6 form a stable heterodimer."

reach
"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."

reach
"38 Also the MPN domain is involved in heterodimerization between CSN6 and CSN5 to regulate Cullin neddylation."

reach
"However, in the CSN5-CSN6 heterodimer, CSN5i-3 forms stable H-bonds with both Thr154 and Asn158 (Figure S5D and Figure 13B)."

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."

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)."

sparser
"Structurally, CSN6 and CSN5 form a heterodimer through MPN domain, and the dimer is topologically knotted to engage in Cullin deneddylation ( xref )."

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."

No evidence text available

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)."

No evidence text available

sparser
"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 )."

sparser
"Sitting atop…is the CSN5CSN6 tomato….” [ xref ])."

reach
"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."

reach
"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."

No evidence text available