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- PDB-8t9h: 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: 8t9h | |||||||||||||||
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Title | Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1 | |||||||||||||||
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![]() | GENE REGULATION / Chromatin / Histone H4 modification / Methyltransferase | |||||||||||||||
Function / homology | ![]() histone H4K20me methyltransferase activity / [histone H4]-N-methyl-L-lysine20 N-methyltransferase / histone H4K20 monomethyltransferase activity / [histone H4]-lysine20 N-methyltransferase / histone H4K20 methyltransferase activity / histone H4 methyltransferase activity / positive regulation of isotype switching / condensed chromosome, centromeric region / S-adenosyl-L-methionine binding / muscle organ development ...histone H4K20me methyltransferase activity / [histone H4]-N-methyl-L-lysine20 N-methyltransferase / histone H4K20 monomethyltransferase activity / [histone H4]-lysine20 N-methyltransferase / histone H4K20 methyltransferase activity / histone H4 methyltransferase activity / positive regulation of isotype switching / condensed chromosome, centromeric region / S-adenosyl-L-methionine binding / muscle organ development / histone methyltransferase activity / positive regulation of double-strand break repair via nonhomologous end joining / PKMTs methylate histone lysines / structural constituent of chromatin / nucleosome / nucleosome assembly / methylation / protein heterodimerization activity / DNA repair / chromatin binding / DNA binding / nucleoplasm / nucleus / metal ion binding Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() Escherichia coli 'BL21-GoldpLysS AG' | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.37 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 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 Simon / Jean-Paul Armache / Evgeny Nudler / Geeta Narlikar / Shixin Liu / Chao Lu / Karim-Jean Armache / ![]() Abstract: The intricate regulation of chromatin plays a key role in controlling genome architecture and accessibility. Histone lysine methyltransferases regulate chromatin by catalyzing the methylation of ...The intricate regulation of chromatin plays a key role in controlling genome architecture and accessibility. Histone lysine methyltransferases regulate chromatin by catalyzing the methylation of specific histone residues but are also hypothesized to have equally important non-catalytic roles. SUV420H1 di- and tri-methylates histone H4 lysine 20 (H4K20me2/me3) and plays crucial roles in DNA replication, repair, and heterochromatin formation, and 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 the enzyme likely has uncharacterized non-catalytic activities. To characterize the catalytic and non-catalytic mechanisms SUV420H1 uses to modify chromatin, we determined cryo- EM structures of SUV420H1 complexes with nucleosomes containing histone H2A or its variant H2A.Z. Our structural, biochemical, biophysical, and cellular analyses reveal how both SUV420H1 recognizes its substrate and H2A.Z stimulates its activity, and show that SUV420H1 binding to nucleosomes causes a dramatic detachment of nucleosomal DNA from histone octamer. We hypothesize that this detachment increases DNA accessibility to large macromolecular complexes, a prerequisite for DNA replication and repair. We also show that SUV420H1 can promote chromatin condensates, another non-catalytic role 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 | ![]() | 302.5 KB | Display | ![]() |
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PDB format | ![]() | 224.8 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 | ![]() | 43.1 KB | Display | |
Data in CIF | ![]() | 64.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 41111MC 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 , 5 types, 9 molecules AEBFCGDHK
#1: 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 #2: Protein | Mass: 11396.442 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: A0A8J1LTD2 #3: Protein | Mass: 14109.436 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: Q6AZJ8 #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 #7: Protein | | Mass: 44703.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() References: UniProt: Q4FZB7 |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 44824.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() |
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#6: DNA chain | Mass: 45304.863 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() |
-Details
Has ligand of interest | Y |
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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: SUV420H1-H2A.Z nucleosome complex / Type: COMPLEX / Entity ID: #7, #5-#6, #2, #1 / 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: 3.37 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 366390 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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