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- PDB-8thu: Catalytic and non-catalytic mechanisms of histone H4 lysine 20 me... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8thu | |||||||||||||||
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Title | Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1 | |||||||||||||||
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![]() | GENE REGULATION/DNA / Chromatin / Histone H4 modification / Methyltransferase / GENE REGULATION / GENE REGULATION-DNA complex | |||||||||||||||
Function / homology | ![]() RNA polymerase II core promoter sequence-specific DNA binding / heterochromatin / nucleosomal DNA binding / cellular response to estradiol stimulus / euchromatin / heterochromatin formation / chromatin DNA binding / structural constituent of chromatin / nucleosome / nucleosome assembly ...RNA polymerase II core promoter sequence-specific DNA binding / heterochromatin / nucleosomal DNA binding / cellular response to estradiol stimulus / euchromatin / heterochromatin formation / chromatin DNA binding / structural constituent of chromatin / nucleosome / nucleosome assembly / chromatin organization / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein heterodimerization activity / Amyloid fiber formation / positive regulation of transcription by RNA polymerase II / DNA binding / extracellular exosome / nucleoplasm / nucleus Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() synthetic construct (others) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||
![]() | Abini-Agbomson, S. / Armache, K.-J. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1. Authors: Stephen Abini-Agbomson / Kristjan Gretarsson / Rochelle M Shih / Laura Hsieh / Tracy Lou / Pablo De Ioannes / Nikita Vasilyev / Rachel Lee / Miao Wang / Matthew D Simon / Jean-Paul Armache / ...Authors: Stephen Abini-Agbomson / Kristjan Gretarsson / Rochelle M Shih / Laura Hsieh / Tracy Lou / Pablo De Ioannes / Nikita Vasilyev / Rachel Lee / Miao Wang / Matthew D Simon / Jean-Paul Armache / Evgeny Nudler / Geeta Narlikar / Shixin Liu / Chao Lu / Karim-Jean Armache / ![]() Abstract: SUV420H1 di- and tri-methylates histone H4 lysine 20 (H4K20me2/H4K20me3) and plays crucial roles in DNA replication, repair, and heterochromatin formation. It is dysregulated in several cancers. Many ...SUV420H1 di- and tri-methylates histone H4 lysine 20 (H4K20me2/H4K20me3) and plays crucial roles in DNA replication, repair, and heterochromatin formation. It is dysregulated in several cancers. Many of these processes were linked to its catalytic activity. However, deletion and inhibition of SUV420H1 have shown distinct phenotypes, suggesting that the enzyme likely has uncharacterized non-catalytic activities. Our cryoelectron microscopy (cryo-EM), biochemical, biophysical, and cellular analyses reveal how SUV420H1 recognizes its nucleosome substrates, and how histone variant H2A.Z stimulates its catalytic activity. SUV420H1 binding to nucleosomes causes a dramatic detachment of nucleosomal DNA from the histone octamer, which is a non-catalytic activity. We hypothesize that this regulates the accessibility of large macromolecular complexes to chromatin. We show that SUV420H1 can promote chromatin condensation, another non-catalytic activity that we speculate is needed for its heterochromatin functions. Together, our studies uncover and characterize the catalytic and non-catalytic mechanisms of SUV420H1, a key histone methyltransferase that plays an essential role in genomic stability. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 314.2 KB | Display | ![]() |
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PDB format | ![]() | 237.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 41272MC ![]() 8t9fC 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 , 4 types, 8 molecules GCAEBFDH
#1: Protein | Mass: 13581.796 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: P0C0S5 #2: Protein | Mass: 15303.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: P84233 #3: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: A0A8J1LTD2 #4: Protein | Mass: 13655.948 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: P02281 |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 44824.570 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA chain | Mass: 45304.863 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-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: SUV420H1-H2A.Z nucleosome complex / Type: COMPLEX / Entity ID: #1-#4, #6, #5 / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Source (natural) | Organism: ![]() | ||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||
Buffer solution | pH: 7.9 / Details: 50 mM HEPES pH 7.9, 100 mM NaCl, 2 mM DTT | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 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: 2400 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: cryoSPARC / Category: particle selection | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 206872 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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