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- PDB-8jhg: Native SUV420H1 bound to 167-bp nucleosome -

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Basic information

Entry
Database: PDB / ID: 8jhg
TitleNative SUV420H1 bound to 167-bp nucleosome
Components
  • (DNA (160-MER)) x 2
  • Histone H2A type 1-B/E
  • Histone H2B type 1-K
  • Histone H3.1
  • Histone H4
  • Histone-lysine N-methyltransferase KMT5B
KeywordsGENE REGULATION/DNA / nucleosome complex / histone methyltransferase / GENE REGULATION-DNA complex
Function / homology
Function and homology information


[histone H4]-N-methyl-L-lysine20 N-methyltransferase / histone H4K20me methyltransferase activity / [histone H4]-lysine20 N-methyltransferase / histone H4K20 monomethyltransferase activity / histone H4K20 methyltransferase activity / histone H4 methyltransferase activity / positive regulation of isotype switching / condensed chromosome, centromeric region / S-adenosyl-L-methionine binding / positive regulation of double-strand break repair via nonhomologous end joining ...[histone H4]-N-methyl-L-lysine20 N-methyltransferase / histone H4K20me methyltransferase activity / [histone H4]-lysine20 N-methyltransferase / histone H4K20 monomethyltransferase activity / histone H4K20 methyltransferase activity / histone H4 methyltransferase activity / positive regulation of isotype switching / condensed chromosome, centromeric region / S-adenosyl-L-methionine binding / positive regulation of double-strand break repair via nonhomologous end joining / muscle organ development / histone methyltransferase activity / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / telomere organization / Meiotic synapsis / Interleukin-7 signaling / RNA Polymerase I Promoter Opening / epigenetic regulation of gene expression / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / G2/M DNA damage checkpoint / HDMs demethylate histones / B-WICH complex positively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / heterochromatin formation / PKMTs methylate histone lysines / Metalloprotease DUBs / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / UCH proteinases / antimicrobial humoral immune response mediated by antimicrobial peptide / nucleosome / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / antibacterial humoral response / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / Processing of DNA double-strand break ends / gene expression / Senescence-Associated Secretory Phenotype (SASP) / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium / Estrogen-dependent gene expression / methylation / killing of cells of another organism / chromosome, telomeric region / Ub-specific processing proteases / defense response to Gram-positive bacterium / cadherin binding / protein heterodimerization activity / Amyloid fiber formation / negative regulation of cell population proliferation / DNA repair / chromatin binding / protein-containing complex / DNA binding / RNA binding / extracellular space / extracellular exosome / extracellular region
Similarity search - Function
KMT5B , SET domain / Suv4-20 family, animal / Histone-lysine N-methyltransferase Suv4-20/Set9 / Histone-lysine N-methyltransferase, N-terminal domain / Histone-lysine N-methyltransferase (EC 2.1.1.43) family profile. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain / SET domain superfamily / SET domain profile. / SET domain ...KMT5B , SET domain / Suv4-20 family, animal / Histone-lysine N-methyltransferase Suv4-20/Set9 / Histone-lysine N-methyltransferase, N-terminal domain / Histone-lysine N-methyltransferase (EC 2.1.1.43) family profile. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain / SET domain superfamily / SET domain profile. / SET domain / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / Histone H2A / Histone 2A / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Histone-fold
Similarity search - Domain/homology
S-ADENOSYLMETHIONINE / DNA / DNA (> 10) / DNA (> 100) / Histone H2B type 1-K / Histone H2A type 1-B/E / Histone H4 / Histone H3.1 / Histone-lysine N-methyltransferase KMT5B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsLin, F. / Li, W.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32200473 China
CitationJournal: Cell Discov / Year: 2023
Title: Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase.
Authors: Folan Lin / Ruxin Zhang / Weihan Shao / Cong Lei / Mingxi Ma / Ying Zhang / Zengqi Wen / Wanqiu Li /
Abstract: Histone lysine methyltransferase SUV420H1, which is responsible for site-specific di-/tri-methylation of histone H4 lysine 20 (H4K20), has crucial roles in DNA-templated processes, including DNA ...Histone lysine methyltransferase SUV420H1, which is responsible for site-specific di-/tri-methylation of histone H4 lysine 20 (H4K20), has crucial roles in DNA-templated processes, including DNA replication, DNA damage repair, and chromatin compaction. Its mutations frequently occur in human cancers. Nucleosomes containing the histone variant H2A.Z enhance the catalytic activities of SUV420H1 on H4K20 di-methylation deposition, regulating early replication origins. However, the molecular mechanism by which SUV420H1 specifically recognizes and deposits H4K20 methyl marks on nucleosomes remains poorly understood. Here we report the cryo-electron microscopy structures of SUV420H1 associated with H2A-containing nucleosome core particles (NCPs), and H2A.Z-containing NCPs. We find that SUV420H1 makes extensive site-specific contacts with histone and DNA regions. SUV420H1 C-terminal domain recognizes the H2A-H2B acidic patch of NCPs through its two arginine anchors, thus enabling H4K20 insertion for catalysis specifically. We also identify important residues increasing the catalytic activities of SUV420H1 bound to H2A.Z NCPs. In vitro and in vivo functional analyses reveal that multiple disease-associated mutations at the interfaces are essential for its catalytic activity and chromatin state regulation. Together, our study provides molecular insights into the nucleosome-based recognition and methylation mechanisms of SUV420H1, and a structural basis for understanding SUV420H1-related human disease.
History
DepositionMay 23, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Nov 22, 2023Provider: repository / Type: Initial release
Revision 1.1Dec 20, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
K: Histone-lysine N-methyltransferase KMT5B
A: Histone H3.1
B: Histone H4
C: Histone H2A type 1-B/E
D: Histone H2B type 1-K
E: Histone H3.1
F: Histone H4
G: Histone H2A type 1-B/E
H: Histone H2B type 1-K
I: DNA (160-MER)
J: DNA (160-MER)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)237,74613
Polymers237,28211
Non-polymers4642
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 5 types, 9 molecules KAEBFCGDH

#1: Protein Histone-lysine N-methyltransferase KMT5B / Lysine N-methyltransferase 5B / Lysine-specific methyltransferase 5B / Suppressor of variegation 4- ...Lysine N-methyltransferase 5B / Lysine-specific methyltransferase 5B / Suppressor of variegation 4-20 homolog 1 / Su(var)4-20 homolog 1 / Suv4-20h1 / [histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B / [histone H4]-lysine20 N-methyltransferase KMT5B


Mass: 41330.703 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KMT5B, SUV420H1, CGI-85 / Production host: Escherichia coli (E. coli)
References: UniProt: Q4FZB7, [histone H4]-N-methyl-L-lysine20 N-methyltransferase, [histone H4]-lysine20 N-methyltransferase
#2: Protein Histone H3.1 / Histone H3/a / Histone H3/b / Histone H3/c / Histone H3/d / Histone H3/f / Histone H3/h / Histone ...Histone H3/a / Histone H3/b / Histone H3/c / Histone H3/d / Histone H3/f / Histone H3/h / Histone H3/i / Histone H3/j / Histone H3/k / Histone H3/l


Mass: 15437.167 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
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: Escherichia coli (E. coli) / References: UniProt: P68431
#3: Protein Histone H4


Mass: 9863.606 Da / Num. of mol.: 2 / Mutation: K20M
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
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: Escherichia coli (E. coli) / Strain (production host): DE3 / References: UniProt: P62805
#4: Protein Histone H2A type 1-B/E / Histone H2A.2 / Histone H2A/a / Histone H2A/m


Mass: 12675.781 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: H2AC4, H2AFM, HIST1H2AB, H2AC8, H2AFA, HIST1H2AE / Production host: Escherichia coli (E. coli) / References: UniProt: P04908
#5: Protein Histone H2B type 1-K / H2B K / HIRA-interacting protein 1


Mass: 10607.174 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: H2BC12, H2BFT, HIRIP1, HIST1H2BK / Production host: Escherichia coli (E. coli) / Strain (production host): DE3 / References: UniProt: O60814

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DNA chain , 2 types, 2 molecules IJ

#6: DNA chain DNA (160-MER)


Mass: 49038.215 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)
#7: DNA chain DNA (160-MER)


Mass: 49745.680 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)

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Non-polymers , 2 types, 2 molecules

#8: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#9: Chemical ChemComp-SAM / S-ADENOSYLMETHIONINE


Mass: 398.437 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H22N6O5S / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Cryo-EM structure of the native SUV420H1 bound to 167-bp nucleosome
Type: COMPLEX / Entity ID: #1-#3, #5 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.246 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli) / Strain: DE3
Buffer solutionpH: 7.5
SpecimenConc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: The sample was monodisperse.
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K
Details: blotted for 3 s before being plunged into liquid ethane

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 0.07 mm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 35448 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00416075
ELECTRON MICROSCOPYf_angle_d0.60923127
ELECTRON MICROSCOPYf_dihedral_angle_d30.2524525
ELECTRON MICROSCOPYf_chiral_restr0.0362604
ELECTRON MICROSCOPYf_plane_restr0.0041778

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