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Open data
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Basic information
Entry | Database: PDB / ID: 8svf | ||||||||||||
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Title | BAP1/ASXL1 bound to the H2AK119Ub Nucleosome | ||||||||||||
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![]() | NUCLEAR PROTEIN/DNA/RNA / DNA complex protein / hydrolase / structural protein / NUCLEAR PROTEIN-DNA-RNA complex | ||||||||||||
Function / homology | ![]() thrombocyte differentiation / nucleate erythrocyte differentiation / PR-DUB complex / platelet morphogenesis / histone H2A deubiquitinase activity / positive regulation of retinoic acid receptor signaling pathway / lung saccule development / macrophage homeostasis / leukocyte proliferation / podocyte development ...thrombocyte differentiation / nucleate erythrocyte differentiation / PR-DUB complex / platelet morphogenesis / histone H2A deubiquitinase activity / positive regulation of retinoic acid receptor signaling pathway / lung saccule development / macrophage homeostasis / leukocyte proliferation / podocyte development / negative regulation of peroxisome proliferator activated receptor signaling pathway / myeloid cell apoptotic process / regulation of kidney size / neutrophil differentiation / hematopoietic stem cell homeostasis / common myeloid progenitor cell proliferation / monoubiquitinated protein deubiquitination / protein K48-linked deubiquitination / tissue homeostasis / nuclear retinoic acid receptor binding / peroxisome proliferator activated receptor binding / bone marrow development / positive regulation of protein targeting to mitochondrion / erythrocyte maturation / negative regulation of fat cell differentiation / regulation of cytokine production involved in inflammatory response / hemopoiesis / homeostasis of number of cells / protein deubiquitination / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / response to retinoic acid / heart morphogenesis / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of FZD by ubiquitination / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / APC-Cdc20 mediated degradation of Nek2A / InlA-mediated entry of Listeria monocytogenes into host cells / Regulation of pyruvate metabolism / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Pexophagy / VLDLR internalisation and degradation / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / InlB-mediated entry of Listeria monocytogenes into host cell / Translesion synthesis by POLK / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / TICAM1, RIP1-mediated IKK complex recruitment / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / IKK complex recruitment mediated by RIP1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / Regulation of activated PAK-2p34 by proteasome mediated degradation / TNFR1-induced NF-kappa-B signaling pathway / PINK1-PRKN Mediated Mitophagy / TCF dependent signaling in response to WNT / Autodegradation of Cdh1 by Cdh1:APC/C / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / APC/C:Cdc20 mediated degradation of Securin / activated TAK1 mediates p38 MAPK activation / Regulation of NF-kappa B signaling / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / Regulation of signaling by CBL / NIK-->noncanonical NF-kB signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / SCF-beta-TrCP mediated degradation of Emi1 Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() synthetic construct (others) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
![]() | Thomas, J.F. / Valencia-Sanchez, M.I. / Armache, K.-J. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1. Authors: Jonathan F Thomas / Marco Igor Valencia-Sánchez / Simone Tamburri / Susan L Gloor / Samantha Rustichelli / Victoria Godínez-López / Pablo De Ioannes / Rachel Lee / Stephen Abini-Agbomson ...Authors: Jonathan F Thomas / Marco Igor Valencia-Sánchez / Simone Tamburri / Susan L Gloor / Samantha Rustichelli / Victoria Godínez-López / Pablo De Ioannes / Rachel Lee / Stephen Abini-Agbomson / Kristjan Gretarsson / Jonathan M Burg / Allison R Hickman / Lu Sun / Saarang Gopinath / Hailey F Taylor / Zu-Wen Sun / Ryan J Ezell / Anup Vaidya / Matthew J Meiners / Marcus A Cheek / William J Rice / Vladimir Svetlov / Evgeny Nudler / Chao Lu / Michael-Christopher Keogh / Diego Pasini / Karim-Jean Armache / ![]() ![]() Abstract: Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated by Polycomb repressive deubiquitinase complex (PR-DUB). PR-DUB cleaves H2AK119Ub to ...Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated by Polycomb repressive deubiquitinase complex (PR-DUB). PR-DUB cleaves H2AK119Ub to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. The PR-DUB subunits (BAP1 and ASXL1) are among the most frequently mutated epigenetic factors in human cancers. How PR-DUB establishes specificity for H2AK119Ub over other nucleosomal ubiquitination sites and how disease-associated mutations of the enzyme affect activity are unclear. Here, we determine a cryo-EM structure of human BAP1 and the ASXL1 DEUBAD in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for restructuring the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing insight into understanding cancer etiology. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 406.6 KB | Display | ![]() |
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PDB format | ![]() | 282.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 50.8 KB | Display | |
Data in CIF | ![]() | 79 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 40789MC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 7 types, 11 molecules AEBFCGDHKLM
#1: Protein | Mass: 15435.126 Da / Num. of mol.: 2 / Mutation: G103A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 14093.436 Da / Num. of mol.: 2 / Mutation: G100R, K120C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 13979.291 Da / Num. of mol.: 2 / Mutation: S33T Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | | Mass: 80472.617 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #8: Protein | | Mass: 165635.203 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #9: Protein | | Mass: 8576.831 Da / Num. of mol.: 1 / Mutation: G76C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-DNA/RNA hybrid , 2 types, 2 molecules IJ
#5: DNA/RNA hybrid | Mass: 58568.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA/RNA hybrid | Mass: 102866.516 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Details
Has protein modification | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: BAP1/ASXL1 bound to the H2AK119Ub Nucleosome / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||
Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1900 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 57.12 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 39056 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1
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Refine LS restraints |
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