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Yorodumi- EMDB-40790: Map focused on acidic patch BAP1/ASXL1 bound to the H2AK119Ub Nuc... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40790 | ||||||||||||
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Title | Map focused on acidic patch BAP1/ASXL1 bound to the H2AK119Ub Nucleosome | ||||||||||||
Map data | Main map focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map resampled in the direction of EMD-40789. | ||||||||||||
Sample |
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Keywords | DNA complex protein / hydrolase / structural protein / NUCLEAR PROTEIN-DNA complex | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
Authors | Thomas JF / Valencia-Sanchez MI | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Sci Adv / Year: 2023 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40790.map.gz | 49.6 MB | EMDB map data format | |
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Header (meta data) | emd-40790-v30.xml emd-40790.xml | 26.8 KB 26.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40790_fsc.xml | 10.4 KB | Display | FSC data file |
Images | emd_40790.png | 104.6 KB | ||
Masks | emd_40790_msk_1.map | 103 MB | Mask map | |
Others | emd_40790_additional_1.map.gz emd_40790_additional_2.map.gz emd_40790_additional_3.map.gz emd_40790_additional_4.map.gz emd_40790_half_map_1.map.gz emd_40790_half_map_2.map.gz | 51.5 MB 95.5 MB 1.5 MB 95.5 MB 80.9 MB 80.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40790 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40790 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_40790.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Main map focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map resampled in the direction of EMD-40789. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.99 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40790_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Main map without resampling focused on acidic patch...
File | emd_40790_additional_1.map | ||||||||||||
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Annotation | Main map without resampling focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Half map A focused on acidic patch of...
File | emd_40790_additional_2.map | ||||||||||||
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Annotation | Half map A focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map without resampling. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Mask for map focused on acidic patch of...
File | emd_40790_additional_3.map | ||||||||||||
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Annotation | Mask for map focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map without resampling. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Half map B focused on acidic patch of...
File | emd_40790_additional_4.map | ||||||||||||
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Annotation | Half map B focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map without resampling. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A focused on acidic patch of...
File | emd_40790_half_map_1.map | ||||||||||||
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Annotation | Half map A focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map resampled in the direction of EMD-40789. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B focused on acidic patch of...
File | emd_40790_half_map_2.map | ||||||||||||
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Annotation | Half map B focused on acidic patch of BAP1/ASXL1 bound to H2AK119Ub nucleosome. Map resampled in the direction of EMD-40789. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : BAP1/ASXL1 bound to the H2AK119Ub Nucleosome
Entire | Name: BAP1/ASXL1 bound to the H2AK119Ub Nucleosome |
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Components |
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-Supramolecule #1: BAP1/ASXL1 bound to the H2AK119Ub Nucleosome
Supramolecule | Name: BAP1/ASXL1 bound to the H2AK119Ub Nucleosome / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#9 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.1 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 0.9 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 57.12 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL |