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Open data
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Basic information
Entry | Database: PDB / ID: 6gvw | ||||||
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Title | Crystal structure of the BRCA1-A complex | ||||||
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![]() | SIGNALING PROTEIN / Deubiquitinase complex / DUB / Lysine-63 linkage specific / BRCC36-containing / BRCA1A binding | ||||||
Function / homology | ![]() : / mitotic G2 DNA damage checkpoint signaling => GO:0007095 / : / BRISC complex / G2/M DNA damage checkpoint / Nonhomologous End-Joining (NHEJ) / Metalloprotease DUBs / Processing of DNA double-strand break ends / BRCA1-A complex / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks ...: / mitotic G2 DNA damage checkpoint signaling => GO:0007095 / : / BRISC complex / G2/M DNA damage checkpoint / Nonhomologous End-Joining (NHEJ) / Metalloprotease DUBs / Processing of DNA double-strand break ends / BRCA1-A complex / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / attachment of spindle microtubules to kinetochore / nuclear ubiquitin ligase complex / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / mitotic G2/M transition checkpoint / tumor necrosis factor receptor binding / protein K63-linked deubiquitination / K63-linked polyubiquitin modification-dependent protein binding / hematopoietic stem cell proliferation / response to ionizing radiation / mitotic G2 DNA damage checkpoint signaling / response to X-ray / mitotic spindle assembly / polyubiquitin modification-dependent protein binding / regulation of DNA repair / nuclear retinoid X receptor binding / enzyme regulator activity / ubiquitin ligase complex / positive regulation of DNA repair / spindle pole / metallopeptidase activity / double-strand break repair / chromatin organization / histone binding / microtubule binding / cysteine-type deubiquitinase activity / nuclear body / cell cycle / cell division / negative regulation of DNA-templated transcription / apoptotic process / DNA damage response / negative regulation of apoptotic process / DNA binding / nucleoplasm / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Bunker, R.D. / Rabl, J. / Thoma, N.H. | ||||||
![]() | ![]() Title: Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation. Authors: Julius Rabl / Richard D Bunker / Andreas D Schenk / Simone Cavadini / Mark E Gill / Wassim Abdulrahman / Amparo Andrés-Pons / Martijn S Luijsterburg / Adel F M Ibrahim / Emma Branigan / ...Authors: Julius Rabl / Richard D Bunker / Andreas D Schenk / Simone Cavadini / Mark E Gill / Wassim Abdulrahman / Amparo Andrés-Pons / Martijn S Luijsterburg / Adel F M Ibrahim / Emma Branigan / Jacob D Aguirre / Aimee H Marceau / Claire Guérillon / Tewis Bouwmeester / Ulrich Hassiepen / Antoine H F M Peters / Martin Renatus / Laurent Gelman / Seth M Rubin / Niels Mailand / Haico van Attikum / Ronald T Hay / Nicolas H Thomä / ![]() ![]() ![]() ![]() ![]() Abstract: In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. ...In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling and contain the lysine-63 linkage-specific BRCC36 subunit that is functionalized by scaffold subunits ABRAXAS and ABRO1, respectively. The molecular basis underlying BRCA1-A and BRISC function is currently unknown. Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2α, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains. Our work explains modularity in the BRCC36 DUB family, with different adaptor subunits conferring diversified targeting and regulatory functions. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.9 MB | Display | ![]() |
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PDB format | ![]() | 1.6 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 512.8 KB | Display | ![]() |
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Full document | ![]() | 532.8 KB | Display | |
Data in XML | ![]() | 82.6 KB | Display | |
Data in CIF | ![]() | 111.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Refine code: _
NCS ensembles :
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Components
-BRCA1-A complex subunit ... , 2 types, 4 molecules AFEJ
#1: Protein | Mass: 46431.422 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 7327.536 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Protein , 1 types, 2 molecules BG
#2: Protein | Mass: 33711.422 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P46737, Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases |
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-BRISC and BRCA1-A complex member ... , 2 types, 4 molecules CHDI
#3: Protein | Mass: 43915.836 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 37155.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 2 types, 4 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/HOH.gif)
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#6: Chemical | #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.81 Å3/Da / Density % sol: 67.71 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop Details: 100 mM MES-KOH pH 5.6, 200 mM MgCl2, 8% (w/v) PEG6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 10, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.75→30 Å / Num. obs: 53796 / % possible obs: 100 % / Observed criterion σ(I): -3 / Redundancy: 51.9 % / Biso Wilson estimate: 163 Å2 / CC1/2: 0.952 / Rmerge(I) obs: 0.173 / Rrim(I) all: 0.175 / Χ2: 1.19 / Net I/σ(I): 11.6 |
Reflection shell | Resolution: 3.75→3.814 Å / Redundancy: 52.8 % / Rmerge(I) obs: 15.709 / Mean I/σ(I) obs: 0.4 / Num. unique obs: 2661 / CC1/2: 0.476 / Rrim(I) all: 15.86 / Χ2: 1.45 / % possible all: 100 |
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Processing
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Refinement | Method to determine structure: ![]()
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Solvent computation | Ion probe radii: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 209.67 Å2
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Refinement step | Cycle: LAST / Resolution: 3.75→29.99 Å
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Refine LS restraints |
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