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Open data
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Basic information
Entry | Database: PDB / ID: 8wg5 | ||||||
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Title | Cryo-EM structure of USP16 bound to H2AK119Ub nucleosome | ||||||
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![]() | NUCLEAR PROTEIN / nucleosome complex / USP16 / H2AK119Ub | ||||||
Function / homology | ![]() mitotic nuclear division / histone H2A deubiquitinase activity / monoubiquitinated protein deubiquitination / positive regulation of translational elongation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / ribosomal small subunit binding / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity ...mitotic nuclear division / histone H2A deubiquitinase activity / monoubiquitinated protein deubiquitination / positive regulation of translational elongation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / ribosomal small subunit binding / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / positive regulation of ribosome biogenesis / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Interleukin-7 signaling / epigenetic regulation of gene expression / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / ubiquitin binding / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / E3 ubiquitin ligases ubiquitinate target proteins / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / gene expression / antibacterial humoral response / histone binding / Oxidative Stress Induced Senescence / protein homotetramerization / defense response to Gram-negative bacterium / Estrogen-dependent gene expression / transcription coactivator activity / killing of cells of another organism / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / regulation of cell cycle / Ub-specific processing proteases / defense response to Gram-positive bacterium / cadherin binding / protein heterodimerization activity / Amyloid fiber formation / cell division / negative regulation of cell population proliferation / cysteine-type endopeptidase activity / DNA damage response / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / protein-containing complex Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.05 Å | ||||||
![]() | Ai, H.S. / He, Z.Z. / Deng, Z.H. / Liu, L. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16. Authors: Huasong Ai / Zaozhen He / Zhiheng Deng / Guo-Chao Chu / Qiang Shi / Zebin Tong / Jia-Bin Li / Man Pan / Lei Liu / ![]() Abstract: Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in ...Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in transcription repression, is dynamically regulated by the opposing activities of Polycomb repressive complex 1 (PRC1) and nucleosome deubiquitinases including the primary human USP16 and Polycomb repressive deubiquitinase (PR-DUB) complex. Recently, the catalytic mechanism for the multi-subunit PR-DUB complex has been described, but how the single-subunit USP16 recognizes the H2AK119Ub nucleosome and cleaves the ubiquitin (Ub) remains unknown. Here we report the cryo-EM structure of USP16-H2AK119Ub nucleosome complex, which unveils a fundamentally distinct mode of H2AK119Ub deubiquitination compared to PR-DUB, encompassing the nucleosome recognition pattern independent of the H2A-H2B acidic patch and the conformational heterogeneity in the Ub motif and the histone H2A C-terminal tail. Our work highlights the mechanism diversity of H2AK119Ub deubiquitination and provides a structural framework for understanding the disease-causing mutations of USP16. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 357.8 KB | Display | ![]() |
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PDB format | ![]() | 267.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 50 KB | Display | |
Data in CIF | ![]() | 78.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 37503MC M: map data used to model this data C: citing same article ( |
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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 , 6 types, 10 molecules MAEBFCGDHU
#1: Protein | Mass: 93708.250 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||||
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#2: Protein | Mass: 11562.577 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, ...Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, HIST1H3I, H3C12, H3FJ, HIST1H3J Production host: ![]() ![]() #3: Protein | Mass: 9010.534 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4C16, H4-16, HIST4H4 Production host: ![]() ![]() #4: Protein | Mass: 12141.195 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 10477.994 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #8: Protein | | Mass: 8622.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-DNA chain , 2 types, 2 molecules IJ
#6: DNA chain | Mass: 45604.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#7: DNA chain | Mass: 45145.754 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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: Complex of USP16 bound to H2AK119Ub nucleosome / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: 1800 nm / Nominal defocus min: 1300 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.05 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 144457 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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