[English] 日本語
Yorodumi
- PDB-6kiw: Cryo-EM structure of human MLL3-ubNCP complex (4.0 angstrom) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6kiw
TitleCryo-EM structure of human MLL3-ubNCP complex (4.0 angstrom)
Components
  • DNA (144-MER)
  • DNA (145-MER)
  • Histone H2A
  • Histone H2B 1.1
  • Histone H3
  • Histone H4
  • Histone-lysine N-methyltransferase 2C
  • Retinoblastoma-binding protein 5
  • Set1/Ash2 histone methyltransferase complex subunit ASH2
  • Ubiquitin
  • WD repeat-containing protein 5
KeywordsTRANSCRIPTION/DNA / histone modification / nucleosome / MLL / TRANSCRIPTION / TRANSCRIPTION-DNA complex
Function / homology
Function and homology information


euchromatin binding / histone H3-K4 monomethylation / histone methyltransferase activity (H3-K4 specific) / [histone H3]-lysine4 N-trimethyltransferase / Set1C/COMPASS complex / MLL3/4 complex / transferase activity, transferring acyl groups / histone H4-K8 acetylation / histone H4-K5 acetylation / Ada2/Gcn5/Ada3 transcription activator complex ...euchromatin binding / histone H3-K4 monomethylation / histone methyltransferase activity (H3-K4 specific) / [histone H3]-lysine4 N-trimethyltransferase / Set1C/COMPASS complex / MLL3/4 complex / transferase activity, transferring acyl groups / histone H4-K8 acetylation / histone H4-K5 acetylation / Ada2/Gcn5/Ada3 transcription activator complex / histone H3-K4 methylation / histone methyltransferase activity / histone H4-K16 acetylation / negative regulation of histone H3-K4 methylation / beta-catenin-TCF complex assembly / MLL1 complex / positive regulation of histone H3-K4 methylation / positive regulation of gluconeogenesis / nuclear euchromatin / hemopoiesis / SRP-dependent cotranslational protein targeting to membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / viral transcription / histone acetyltransferase complex / translational initiation / histone H3 acetylation / MyD88-independent toll-like receptor signaling pathway / nucleotide-binding oligomerization domain containing signaling pathway / nucleotide-excision repair, DNA gap filling / histone methyltransferase complex / nucleotide-excision repair, DNA damage recognition / DNA-templated transcription, initiation / nucleotide-excision repair, DNA duplex unwinding / TRIF-dependent toll-like receptor signaling pathway / methylated histone binding / global genome nucleotide-excision repair / host cell / nucleotide-excision repair, preincision complex assembly / intracellular transport of virus / regulation of megakaryocyte differentiation / MyD88-dependent toll-like receptor signaling pathway / nucleotide-excision repair, DNA incision, 5'-to lesion / endosomal transport / DNA damage response, detection of DNA damage / error-free translesion synthesis / skeletal system development / modification-dependent protein catabolic process / nucleotide-excision repair, DNA incision / protein targeting to peroxisome / JNK cascade / nucleosome / interstrand cross-link repair / protein tag / endocytic vesicle membrane / error-prone translesion synthesis / stress-activated MAPK cascade / regulation of transcription from RNA polymerase II promoter in response to hypoxia / interleukin-1-mediated signaling pathway / I-kappaB kinase/NF-kappaB signaling / transcription-coupled nucleotide-excision repair / viral life cycle / neuron projection development / beta-catenin binding / negative regulation of transforming growth factor beta receptor signaling pathway / translesion synthesis / virion assembly / cytosolic small ribosomal subunit / transforming growth factor beta receptor signaling pathway / anaphase-promoting complex-dependent catabolic process / transmembrane transport / small ribosomal subunit / regulation of mRNA stability / membrane organization / post-translational protein modification / protein polyubiquitination / histone binding / Wnt signaling pathway / mitochondrial outer membrane / transcription coactivator activity / vesicle / activation of MAPK activity / structural constituent of ribosome / response to estrogen / endosome membrane / transcription regulatory region sequence-specific DNA binding / positive regulation of NF-kappaB transcription factor activity / protein ubiquitination / translation / protein deubiquitination / transcription, DNA-templated / protein heterodimerization activity / positive regulation of apoptotic process / cytokine-mediated signaling pathway / endoplasmic reticulum membrane / cellular response to DNA damage stimulus / nucleolus / cellular protein metabolic process / ubiquitin protein ligase binding / regulation of transcription, DNA-templated / positive regulation of cell population proliferation
Histone H2A, C-terminal domain / Histone H2B / Zinc finger, PHD-type / Histone H4 / B30.2/SPRY domain / Zinc finger, RING-type / C-terminus of histone H2A / WD40 repeat / SET domain / HMG-I/HMG-Y, DNA-binding, conserved site ...Histone H2A, C-terminal domain / Histone H2B / Zinc finger, PHD-type / Histone H4 / B30.2/SPRY domain / Zinc finger, RING-type / C-terminus of histone H2A / WD40 repeat / SET domain / HMG-I/HMG-Y, DNA-binding, conserved site / Ubiquitin-like domain / Core histone H2A/H2B/H3/H4 / Histone H3/CENP-A / S27a-like superfamily / Centromere kinetochore component CENP-T histone fold / Extended PHD (ePHD) domain / CENP-T/Histone H4, histone fold / KMT2C, ePHD2 / WD40-repeat-containing domain superfamily / High mobility group box domain superfamily / Histone methyltransferase complex subunit ASH2 / Retinoblastoma-binding protein 5/Swd1 / WD40-repeat-containing protein Swd3/WDR5 / Histone H2A conserved site / Histone-lysine N-methyltransferase 2C / Histone H2A / Ribosomal protein S27a / SET domain / WD domain, G-beta repeat / Ubiquitin-like domain superfamily / G-protein beta WD-40 repeat / Ubiquitin domain / Ubiquitin conserved site / Histone H4, conserved site / Zinc finger, PHD-finger / WD40 repeat, conserved site / WD40-repeat-containing domain / WD40/YVTN repeat-like-containing domain superfamily / Concanavalin A-like lectin/glucanase domain superfamily / Zinc finger, RING/FYVE/PHD-type / KMT2C, ePHD1 / Zinc-binding ribosomal protein / Zinc finger, FYVE/PHD-type / Histone-fold / High mobility group box domain / Histone H2A/H2B/H3 / TATA box binding protein associated factor (TAF) / FY-rich, C-terminal / FY-rich, N-terminal / SPRY domain / SPRY domain / Post-SET domain / Ubiquitin family / SPRY domain / Histone, subunit A / Histone, subunit A / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / Jelly Rolls / Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Retinoblastoma-binding protein 5 / Histone H3 / Histone H2B 1.1 / Histone H2A / Histone H2A type 1 / WD repeat-containing protein 5 / Histone H4 / Ubiquitin-40S ribosomal protein S27a / Set1/Ash2 histone methyltransferase complex subunit ASH2 / Histone H3.2 / Histone-lysine N-methyltransferase 2C
Biological speciesXenopus laevis (African clawed frog)
Homo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å
AuthorsHuang, J. / Xue, H. / Yao, T.
Funding support China, 1items
OrganizationGrant numberCountry
National Science Foundation (China) China
CitationJournal: Nature / Year: 2019
Title: Structural basis of nucleosome recognition and modification by MLL methyltransferases.
Authors: Han Xue / Tonghui Yao / Mi Cao / Guanjun Zhu / Yan Li / Guiyong Yuan / Yong Chen / Ming Lei / Jing Huang /
Abstract: Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and ...Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.
Validation Report
SummaryFull reportAbout validation report
History
DepositionJul 20, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 11, 2019Provider: repository / Type: Initial release
Revision 1.1Sep 18, 2019Group: Data collection / Database references / Category: citation / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 2, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Nov 6, 2019Group: Data collection / Other / Category: cell / Item: _cell.Z_PDB

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-0693
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone H3
B: Histone H4
C: Histone H2A
D: Histone H2B 1.1
E: Histone H3
F: Histone H4
G: Histone H2A
H: Histone H2B 1.1
I: DNA (144-MER)
J: DNA (145-MER)
K: Histone-lysine N-methyltransferase 2C
N: Retinoblastoma-binding protein 5
O: Ubiquitin
R: WD repeat-containing protein 5
T: Set1/Ash2 histone methyltransferase complex subunit ASH2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)385,77716
Polymers385,71215
Non-polymers651
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 9 types, 13 molecules AEBFCGDHKNORT

#1: Protein Histone H3 /


Mass: 15303.930 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: XELAEV_18002543mg / Production host: Escherichia coli (E. coli) / References: UniProt: A0A310TTQ1, UniProt: P84233*PLUS
#2: Protein Histone H4 /


Mass: 11263.231 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799
#3: Protein Histone H2A /


Mass: 13978.241 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: hist1h2aj, LOC494591, XELAEV_18003602mg / Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8, UniProt: P06897*PLUS
#4: Protein Histone H2B 1.1 / H2B1.1


Mass: 13498.715 Da / Num. of mol.: 2 / Mutation: S29T/K117C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281
#7: Protein Histone-lysine N-methyltransferase 2C / Lysine N-methyltransferase 2C / Homologous to ALR protein / Myeloid/lymphoid or mixed-lineage ...Lysine N-methyltransferase 2C / Homologous to ALR protein / Myeloid/lymphoid or mixed-lineage leukemia protein 3


Mass: 23642.941 Da / Num. of mol.: 1 / Mutation: C4708S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KMT2C, HALR, KIAA1506, MLL3 / Production host: Escherichia coli (E. coli)
References: UniProt: Q8NEZ4, histone-lysine N-methyltransferase
#8: Protein Retinoblastoma-binding protein 5 / RBBP-5 / Retinoblastoma-binding protein RBQ-3


Mass: 59223.477 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RBBP5, RBQ3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15291
#9: Protein Ubiquitin /


Mass: 8622.922 Da / Num. of mol.: 1 / Mutation: G76C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RPS27A, UBA80, UBCEP1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62979
#10: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 36635.438 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli (E. coli) / References: UniProt: P61964
#11: Protein Set1/Ash2 histone methyltransferase complex subunit ASH2 / ASH2-like protein


Mass: 60288.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ASH2L, ASH2L1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UBL3

-
DNA chain , 2 types, 2 molecules IJ

#5: DNA chain DNA (144-MER)


Mass: 44217.172 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#6: DNA chain DNA (145-MER)


Mass: 44992.648 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Non-polymers , 1 types, 1 molecules

#12: Chemical ChemComp-ZN / ZINC ION / Zinc


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Human MLL3 complex associated with an H2B-monoubiquitinated nucleosome (4.0 angstrom)COMPLEX#1-#110MULTIPLE SOURCES
2Human MLL3KMT2CCOMPLEX#1-#111RECOMBINANT
3H2B-monoubiquitinated nucleosomeCOMPLEX#1-#111MULTIPLE SOURCES
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Xenopus laevis (African clawed frog)8355
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Escherichia coli (E. coli)562
23Escherichia coli (E. coli)562
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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 FIELDBright-field microscopy
Image recordingElectron dose: 40 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k)

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.13_2998refinement
PHENIX1.13_2998refinement
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 81945 / Symmetry type: POINT
RefinementStereochemistry target values: GeoStd + Monomer Library
Refine LS restraints
Refinement-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.005921207
ELECTRON MICROSCOPYf_angle_d0.864229905
ELECTRON MICROSCOPYf_chiral_restr0.05143371
ELECTRON MICROSCOPYf_plane_restr0.00682785
ELECTRON MICROSCOPYf_dihedral_angle_d19.043511726

+
About Yorodumi

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • New page: Covid-19 featured information page in EM Navigator

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

-
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. New: Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page)
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is "EMD"? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB at PDBe / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more