[English] 日本語
Yorodumi
- EMDB-0695: Cryo-EM structure of human MLL1-NCP complex, binding mode2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-0695
TitleCryo-EM structure of human MLL1-NCP complex, binding mode2
Map data
SampleHuman MLL1 complex associated with an unmodified nucleosome, binding mode 2
  • Human MLL1 complexKMT2A
  • unmodified nucleosome
  • Histone H3
  • Histone H4
  • Histone H2A
  • Histone H2B 1.1
  • (nucleic-acidNucleic acid) x 2
  • Retinoblastoma-binding protein 5
  • Histone-lysine N-methyltransferase 2A
  • WD repeat-containing protein 5
  • Set1/Ash2 histone methyltransferase complex subunit ASH2
  • (ligand) x 2
Function / homology
Function and homology information


RMTs methylate histone arginines / Formation of the beta-catenin:TCF transactivating complex / PKMTs methylate histone lysines / HATs acetylate histones / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Neddylation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Deactivation of the beta-catenin transactivating complex / euchromatin binding ...RMTs methylate histone arginines / Formation of the beta-catenin:TCF transactivating complex / PKMTs methylate histone lysines / HATs acetylate histones / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Neddylation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Deactivation of the beta-catenin transactivating complex / euchromatin binding / regulation of histone H3-K14 acetylation / positive regulation of cellular response to drug / positive regulation of transporter activity / negative regulation of DNA methylation / unmethylated CpG binding / histone methyltransferase activity (H3-K4 specific) / histone H3-K4 trimethylation / Set1C/COMPASS complex / MLL3/4 complex / AT DNA binding / positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter / histone H4-K5 acetylation / histone H4-K8 acetylation / histone H3-K4 methylation / Ada2/Gcn5/Ada3 transcription activator complex / regulation of histone H3-K9 acetylation / histone H4-K16 acetylation / positive regulation of histone H3-K4 methylation / MLL1 complex / embryonic hemopoiesis / beta-catenin-TCF complex assembly / nuclear euchromatin / hemopoiesis / histone acetyltransferase complex / histone-lysine N-methyltransferase / regulation of hematopoietic stem cell differentiation / histone H3 acetylation / DNA-templated transcription, initiation / methylated histone binding / lysine-acetylated histone binding / histone methyltransferase complex / RNA polymerase II distal enhancer sequence-specific DNA binding / skeletal system development / regulation of megakaryocyte differentiation / nucleosome / circadian regulation of gene expression / neuron projection development / beta-catenin binding / protein-containing complex assembly / post-translational protein modification / transcription by RNA polymerase II / histone binding / transcription regulatory region DNA binding / response to estrogen / transcription, DNA-templated / DNA-binding transcription factor activity, RNA polymerase II-specific / apoptotic process / cellular response to DNA damage stimulus / regulation of transcription, DNA-templated / DNA-binding transcription factor activity / nucleolus / positive regulation of cell population proliferation / protein heterodimerization activity / positive regulation of transcription, DNA-templated / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / metal ion binding / nucleus / cytosol
Post-SET domain / WD40 repeat / FY-rich, C-terminal / FY-rich, N-terminal / SPRY domain / Zinc finger, CXXC-type / Histone H2A / Zinc finger, PHD-type / Histone H4 / B30.2/SPRY domain ...Post-SET domain / WD40 repeat / FY-rich, C-terminal / FY-rich, N-terminal / SPRY domain / Zinc finger, CXXC-type / Histone H2A / Zinc finger, PHD-type / Histone H4 / B30.2/SPRY domain / Bromodomain / Histone H2A/H2B/H3 / SET domain / Histone H2B / Histone H3/CENP-A / KMT2A, PHD domain 2 / Core histone H2A/H2B/H3/H4 / WD domain, G-beta repeat / KMT2A, PHD domain 1 / SPRY domain / PHD-finger / TATA box binding protein associated factor (TAF) / Histone-fold / CXXC zinc finger domain / Histone H2A conserved site / Histone-lysine N-methyltransferase 2A / WD40-repeat-containing protein Swd3/WDR5 / Retinoblastoma-binding protein 5/Swd1 / Histone methyltransferase complex subunit ASH2 / Bromodomain-like superfamily / WD40-repeat-containing domain superfamily / CENP-T/Histone H4, histone fold / Extended PHD (ePHD) domain / Histone H2A, C-terminal domain / Zinc finger, FYVE/PHD-type / G-protein beta WD-40 repeat / Histone H4, conserved site / Zinc finger, PHD-finger / WD40 repeat, conserved site / WD40-repeat-containing domain / Methyltransferase, trithorax / WD40/YVTN repeat-like-containing domain superfamily / Concanavalin A-like lectin/glucanase domain superfamily / Zinc finger, RING/FYVE/PHD-type / SET domain / KMT2A, ePHD domain / F/Y-rich N-terminus / Trp-Asp (WD) repeats profile. / Histone H2B signature. / Trp-Asp (WD) repeats signature. / Histone H3 signature 2. / Zinc finger PHD-type signature. / Bromodomain profile. / Zinc finger PHD-type profile. / B30.2/SPRY domain profile. / Histone H3 signature 1. / SET domain profile. / Trp-Asp (WD) repeats circular profile. / Post-SET domain profile. / Zinc finger CXXC-type profile. / FYR domain FYRN motif profile. / FYR domain FYRC motif profile. / Extended PHD (ePHD) domain profile. / Histone H4 signature. / F/Y rich C-terminus / Histone H2A signature. / Centromere kinetochore component CENP-T histone fold / C-terminus of histone H2A
Histone H3 / Histone H2B 1.1 / WD repeat-containing protein 5 / Histone H4 / Histone-lysine N-methyltransferase 2A / Retinoblastoma-binding protein 5 / Histone H2A / Set1/Ash2 histone methyltransferase complex subunit ASH2
Biological speciesHomo sapiens (human) / Xenopus laevis (African clawed frog) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.5 Å
AuthorsHuang J / Xue H / Yao T
Funding support China, 1 items
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 ReportPDB-ID: 6kiz

SummaryFull reportAbout validation report
History
DepositionJul 20, 2019-
Header (metadata) releaseSep 11, 2019-
Map releaseSep 11, 2019-
UpdateSep 18, 2019-
Current statusSep 18, 2019Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.007
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.007
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: : PDB-6kiz
  • Surface level: 0.007
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_0695.map.gz / Format: CCP4 / Size: 75.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 270 pix.
= 297. Å
1.1 Å/pix.
x 270 pix.
= 297. Å
1.1 Å/pix.
x 270 pix.
= 297. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density
Contour LevelBy AUTHOR: 0.005 / Movie #1: 0.007
Minimum - Maximum-0.05955387 - 0.100226186
Average (Standard dev.)-0.00002088993 (±0.0038999624)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions270270270
Spacing270270270
CellA=B=C: 297.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.11.11.1
M x/y/z270270270
origin x/y/z0.0000.0000.000
length x/y/z297.000297.000297.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS270270270
D min/max/mean-0.0190.044-0.000

-
Supplemental data

-
Sample components

+
Entire Human MLL1 complex associated with an unmodified nucleosome, bind...

EntireName: Human MLL1 complex associated with an unmodified nucleosome, binding mode 2
Number of components: 15

+
Component #1: protein, Human MLL1 complex associated with an unmodified nucleos...

ProteinName: Human MLL1 complex associated with an unmodified nucleosome, binding mode 2
Recombinant expression: No

+
Component #2: protein, Human MLL1 complex

ProteinName: Human MLL1 complexKMT2A / Recombinant expression: No
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #3: protein, unmodified nucleosome

ProteinName: unmodified nucleosome / Recombinant expression: No
SourceSpecies: Xenopus laevis (African clawed frog)

+
Component #4: protein, Histone H3

ProteinName: Histone H3 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 15.30393 kDa
SourceSpecies: Xenopus laevis (African clawed frog)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #5: protein, Histone H4

ProteinName: Histone H4 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 11.263231 kDa
SourceSpecies: Xenopus laevis (African clawed frog)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #6: protein, Histone H2A

ProteinName: Histone H2A / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 13.978241 kDa
SourceSpecies: Xenopus laevis (African clawed frog)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #7: protein, Histone H2B 1.1

ProteinName: Histone H2B 1.1 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 13.498715 kDa
SourceSpecies: Xenopus laevis (African clawed frog)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #8: nucleic-acid, DNA (145-MER)

nucleic acidName: DNA (145-MER) / Class: DNA / Structure: OTHER / Synthetic: No
Sequence:
(DT)(DC)(DG)(DA)(DG)(DA)(DA)(DT)(DC)(DC) (DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA)(DG) (DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA)(DA)(DT) (DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA)(DG)(DA) (DC)(DA)(DG)(DC)(DT)(DC)(DT)(DA)(DG)(DC) (DA)(DC)(DC)(DG)(DC)(DT)(DT)(DA)(DA)(DA) (DC)(DG)(DC)(DA)(DC)(DG)(DT)(DA)(DC)(DG) (DC)(DG)(DC)(DT)(DG)(DT)(DC)(DC)(DC)(DC) (DC)(DG)(DC)(DG)(DT)(DT)(DT)(DT)(DA)(DA) (DC)(DC)(DG)(DC)(DC)(DA)(DA)(DG)(DG)(DG) (DG)(DA)(DT)(DT)(DA)(DC)(DT)(DC)(DC)(DC) (DT)(DA)(DG)(DT)(DC)(DT)(DC)(DC)(DA)(DG) (DG)(DC)(DA)(DC)(DG)(DT)(DG)(DT)(DC)(DA) (DG)(DA)(DT)(DA)(DT)(DA)(DT)(DA)(DC)(DA) (DT)(DC)(DC)(DG)(DA)
MassTheoretical: 44.521367 kDa
SourceSpecies: synthetic construct (others)

+
Component #9: nucleic-acid, DNA (145-MER)

nucleic acidName: DNA (145-MER) / Class: DNA / Structure: OTHER / Synthetic: No
Sequence:
(DT)(DC)(DG)(DG)(DA)(DT)(DG)(DT)(DA)(DT) (DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC)(DA) (DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG)(DG)(DA) (DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG)(DA)(DG) (DT)(DA)(DA)(DT)(DC)(DC)(DC)(DC)(DT)(DT) (DG)(DG)(DC)(DG)(DG)(DT)(DT)(DA)(DA)(DA) (DA)(DC)(DG)(DC)(DG)(DG)(DG)(DG)(DG)(DA) (DC)(DA)(DG)(DC)(DG)(DC)(DG)(DT)(DA)(DC) (DG)(DT)(DG)(DC)(DG)(DT)(DT)(DT)(DA)(DA) (DG)(DC)(DG)(DG)(DT)(DG)(DC)(DT)(DA)(DG) (DA)(DG)(DC)(DT)(DG)(DT)(DC)(DT)(DA)(DC) (DG)(DA)(DC)(DC)(DA)(DA)(DT)(DT)(DG)(DA) (DG)(DC)(DG)(DG)(DC)(DC)(DT)(DC)(DG)(DG) (DC)(DA)(DC)(DC)(DG)(DG)(DG)(DA)(DT)(DT) (DC)(DT)(DC)(DG)(DA)
MassTheoretical: 44.992648 kDa
SourceSpecies: synthetic construct (others)

+
Component #10: protein, Retinoblastoma-binding protein 5

ProteinName: Retinoblastoma-binding protein 5 / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 59.223477 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #11: protein, Histone-lysine N-methyltransferase 2A

ProteinName: Histone-lysine N-methyltransferase 2A / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 24.970539 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #12: protein, WD repeat-containing protein 5

ProteinName: WD repeat-containing protein 5 / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 36.635438 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #13: protein, Set1/Ash2 histone methyltransferase complex subunit ASH2

ProteinName: Set1/Ash2 histone methyltransferase complex subunit ASH2
Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 60.288758 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli (E. coli)

+
Component #14: ligand, S-ADENOSYL-L-HOMOCYSTEINE

LigandName: S-ADENOSYL-L-HOMOCYSTEINE / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 0.384411 kDa

+
Component #15: ligand, ZINC ION

LigandName: ZINC ION / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 6.540905 MDa

-
Experimental details

-
Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 45 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD
Specimen HolderModel: OTHER
CameraDetector: OTHER

-
Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: C1 (asymmetric) / Number of projections: 31882
3D reconstructionResolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF

-
Atomic model buiding

Output model

+
About Yorodumi

-
News

-
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

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

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