IndraLab

Statements

BRCC3 binds ABRAXAS2. 25 / 47
19 | 25
reach
"Moreover, besides interacting with CCDC98 within the BRCA1-A complex, BRCC36 also associates with another protein KIAA0157, which shares significant sequence homology with CCDC98."
20656690
reach
"The association between ABRAXAS2 and BRCC3 and NLRP3 depends on the phosphorylation of NLRP3 serine 194 and the NLRP3 interactor NIMA-related kinase 7 (NEK7), which acts as a scaffold for bridging adjacent NLRP3 subunits and requires proposed priming [124,125]."
36551253
reach
"Structural studies indicate that BRCC36 and ABRAXAS2 or ABRO1 form heterodimers, which ensure enzymatic activity and association with additional cofactors including RAP80 and BRCA1 (in the BRCA1-A complex) or the serine hydroxymethyltransferase 2 (SHMT2) (in the BRISC complex) (107, 108, 109)."
35764170
reach
"Finally, we also show that Abro1, another BRISC subunit, binds directly to Brcc36 and that the Brcc36 and Abro1 heterodimer includes a minimal complex with Lys (63)-specific DUB activity."
20032457
reach
"This mechanism is homologous to what has been observed in the ancestral BRCC36-KIAA0157 complex (Zeqiraj et al., 2015) but is distinct from that seen in the COP9 signalosome (CSN) and the proteasome lid, where the position of the scaffold MPN domain differs (Figure S3B) (Lingaraju et al., 2014, Pathare et al., 2014, Worden et al., 2014, Worden et al., 2017)."
31253574
reach
"Based on current reports, JAMM subunit interfaces are surprisingly diverse in structure and have a variety of roles including function in : i) the assembly of multisubunit complexes and ii) maintaining the JAMM and MPN+ domain in an active state, as in the BRCC36 and KIAA0157 heterodimer."
28479062
reach
"Furthermore, Abro1 binding to BRCC36 promotes the catalytic activity of the enzyme, although this heterodimer has minimal activity when compared to the complete four-subunit BRISC complex [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
21195082
reach
"To understand the basis for BRCC36 regulation, we have solved the structure of an active BRCC36 and KIAA0157 heterodimer and an inactive BRCC36 homodimer."
26344097
reach
"Towards this end, we have characterized the binding architecture of BRISC and ARISC complexes and solved the X-ray crystal structures of the minimally active BRCC36 and KIAA0157 heterodimer subcomplex, and an inactive BRCC36-BRCC36 homodimer complex."
26344097
reach
"Comparison of the BRCC36 and KIAA0157 heterodimer structure with an inactive BRCC36 homodimer structure provides a model for understanding how this functional interplay is achieved."
26344097
reach
"As shown in schematic form in XREF_FIG, the binding of KIAA0157 to BRCC36 is required for stabilization of (1) the CCHB, (2) the E-loop of BRCC36 and optimal positioning of the catalytic glutamate side chain for catalysis, and (3) the Ins-1 loop of BRCC36 and its proper positioning for substrate binding."
26344097
reach
"Stabilization of all three elements is supported through direct interactions between KIAA0157 and BRCC36 within a single heterodimer as well as through interactions across BRCC36-KIAA0157 heterodimers within a super dimer."
26344097
reach
"We pursued crystallization of BRCC36-KIAA0157 subcomplexes from different species (H. sapiens, G. gallus, X. tropicalis, D. rerio, C. floridanus and A. thaliana) to determine the structural basis for (1) how KIAA0157 supports the catalytic function of BRCC36, and (2) how super dimerization of the minimally active BRCC36 and KIAA0157 heterodimer is mediated."
26344097
reach
"Structure of the BRCC36 and KIAA0157 heterodimer."
26344097
reach
"ABRO1 and BRCC36 interaction is required for the DUB activity of BRCC36 in vitro [XREF_BIBR]."
22369660
reach
"Recent cryo-electron microscopy (cryo-EM) structures of the BRISC-SHMT2 complex revealed a U-shaped assembly of the BRISC complex, whereby the BRCC36-Abraxas2 heterodimer bridges two BRCC45-MERIT40 “arms” ."
39282282
reach
"Whilst the BRCC36 and KIAA0157 heterodimer structure was not determined in complex with K63-Ub 2, the K D for binding is 2 muM, the K M for K63-Ub 2 hydrolysis is 4 muM, and the substrate binding surfaces are generally highly conserved."
28587922
reach
"Structural and biochemical analysis of insect Abro1 and BRCC36 complexes has elegantly shown how BRCC36 is allosterically activated by Abro1 binding and how this heterodimeric complex self and associates to form a tight tetrameric assembly, referred to as a " superdimer "."
28009280
reach
"However, and in contrast to insect Abro1 and BRCC36 complexes described previously, the human Abraxas and BRCC36 subcomplex behaved as a soluble aggregate that could not be further purified, but was, nonetheless, able to form a stable monodispersed and stoichiometric assembly when purified in combination with BRCC45 and MERIT40."
28009280
reach
"Structure of the BRCC36 and KIAA0157 heterodimer is functionally relevant in cells."
26344097
reach
"To validate the BRCC36 and KIAA0157 heterodimer as being relevant in cells, we mutated direct contact residues and assessed interaction function of human BRCC36 and KIAA0157 by co-immunoprecipitation (see structure based sequence alignments in XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY for a list of equivalent residues mutated)."
26344097
reach
"Regardless, MALLS analysis of the reconstituted four-component BRCA1-A complex reported an apparent molecular mass of 280kDa (XREF_FIG B), suggestive of a dimer of Abraxas/BRCC36/BRCC45/MERIT40 heterotetramers and consonant with the " super-dimer " originally described for insect Abro1 and BRCC36 heterodimers."
28009280
reach
"However, since both Abraxas and Abro1 each bind to both BRCC36 and BRCC45 in their respective DUB complexes, we surmised that the interaction surfaces for these components should show the highest degree of conservation between the two paralogs."
28009280
reach
"These observations support the notion that the crystal structure of the BRCC36 and KIAA0157 heterodimer is reflective of both BRCC36-KIAA0157 and the BRCC36-Abraxas interactions in cells, and that perturbation of heterodimerization has far reaching consequences on the assembly of other subunits."
26344097
reach
"Curiously, JMS-175-2 and FX-171-C did not inhibit the minimally active BRCC36-Abraxas2 complex, which indicates that the “arm” regions containing BRCC45 and MERIT40 also contribute to the inhibitor selectivity profile (Figs."
39282282