[English] 日本語
Yorodumi
- PDB-7mbm: Cryo-EM structure of MLL1-NCP (H3K4M) complex, mode01 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7mbm
TitleCryo-EM structure of MLL1-NCP (H3K4M) complex, mode01
Components
  • (DNA (145-MER)) x 2
  • Histone H2A
  • Histone H2B 1.1
  • Histone H3
  • Histone H4
  • Histone-lysine N-methyltransferase 2A
  • Retinoblastoma-binding protein 5
  • Set1/Ash2 histone methyltransferase complex subunit ASH2
  • WD repeat-containing protein 5
KeywordsTRANSFERASE/DNA BINDING PROTEIN/DNA / MLL1-NCP / H3K4 methylation / TRANSFERASE / TRANSFERASE-DNA BINDING PROTEIN-DNA complex
Function / homology
Function and homology information


protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex ...protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex / MLL1/2 complex / T-helper 2 cell differentiation / definitive hemopoiesis / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / regulation of embryonic development / hemopoiesis / MLL1 complex / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / transcription initiation-coupled chromatin remodeling / cellular response to transforming growth factor beta stimulus / methylated histone binding / Transferases; Transferring one-carbon groups; Methyltransferases / post-embryonic development / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / euchromatin / lysine-acetylated histone binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / protein modification process / mitotic spindle / PKMTs methylate histone lysines / beta-catenin binding / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / HATs acetylate histones / histone binding / fibroblast proliferation / methylation / protein-containing complex assembly / transcription cis-regulatory region binding / regulation of cell cycle / protein heterodimerization activity / apoptotic process / DNA damage response / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / nucleolus / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol
Similarity search - Function
: / ASH2, PHD zinc finger / Set1/Ash2 histone methyltransferase complex subunit ASH2-like, WH / Histone methyltransferase complex subunit ASH2 / Retinoblastoma-binding protein 5/Swd1 / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax ...: / ASH2, PHD zinc finger / Set1/Ash2 histone methyltransferase complex subunit ASH2-like, WH / Histone methyltransferase complex subunit ASH2 / Retinoblastoma-binding protein 5/Swd1 / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax / : / FY-rich, N-terminal / F/Y-rich N-terminus / PHD-like zinc-binding domain / FYR domain FYRN motif profile. / "FY-rich" domain, N-terminal region / FY-rich, C-terminal / F/Y rich C-terminus / FYR domain FYRC motif profile. / "FY-rich" domain, C-terminal region / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / Cysteine-rich motif following a subset of SET domains / Post-SET domain / Post-SET domain profile. / SPRY domain / B30.2/SPRY domain / B30.2/SPRY domain profile. / SPRY domain / B30.2/SPRY domain superfamily / Domain in SPla and the RYanodine Receptor. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / Extended PHD (ePHD) domain / Extended PHD (ePHD) domain profile. / SET domain profile. / SET domain / PHD-finger / Zinc finger PHD-type signature. / 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 H2A / Histone 2A / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Histone H3 signature 1. / Zinc finger, PHD-type / PHD zinc finger / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Zinc finger, FYVE/PHD-type / Histone-fold / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Concanavalin A-like lectin/glucanase domain superfamily / G-protein beta WD-40 repeat / Zinc finger, RING/FYVE/PHD-type / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
DNA / DNA (> 10) / DNA (> 100) / 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
Similarity search - Component
Biological speciesHomo sapiens (human)
Xenopus laevis (African clawed frog)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM
AuthorsPark, S.H. / Ayoub, A. / Lee, Y.T. / Dou, Y. / Cho, U.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM082856 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA250329 United States
CitationJournal: Biochemistry / Year: 2022
Title: Regulation of MLL1 Methyltransferase Activity in Two Distinct Nucleosome Binding Modes.
Authors: Alex Ayoub / Sang Ho Park / Young-Tae Lee / Uhn-Soo Cho / Yali Dou /
Abstract: Cryo-EM structures of the KMT2A/MLL1 core complex bound on nucleosome core particles (NCPs) suggest unusual rotational dynamics of the MLL1 complex approaching its physiological substrate. However, ...Cryo-EM structures of the KMT2A/MLL1 core complex bound on nucleosome core particles (NCPs) suggest unusual rotational dynamics of the MLL1 complex approaching its physiological substrate. However, the functional implication of such dynamics remains unclear. Here, we show that the MLL1 core complex also shows high rotational dynamics bound on the NCP carrying the catalytically inert histone H3 lysine 4 to methionine (K4M) mutation. There are two major binding modes of the MLL1 complex on the NCP. Importantly, disruption of only one of the binding modes compromised the overall MLL1 activity in an NCP-specific manner. We propose that the MLL1 core complex probably exists in an equilibrium of poised and active binding modes. The high rotational dynamics of the MLL1 complex on the NCP is a feature that can be exploited for loci-specific regulation of H3K4 methylation in higher eukaryotes.
History
DepositionApr 1, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 29, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 19, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 1.2May 29, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-23738
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Retinoblastoma-binding protein 5
B: WD repeat-containing protein 5
C: Histone-lysine N-methyltransferase 2A
D: Set1/Ash2 histone methyltransferase complex subunit ASH2
G: Histone H3
H: Histone H4
I: Histone H2A
J: Histone H2B 1.1
K: Histone H3
L: Histone H4
M: Histone H2A
N: Histone H2B 1.1
O: DNA (145-MER)
P: DNA (145-MER)


Theoretical massNumber of molelcules
Total (without water)377,63714
Polymers377,63714
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: cross-linking
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 8 types, 12 molecules ABCDGKHLIMJN

#1: Protein Retinoblastoma-binding protein 5 / RBBP-5 / Retinoblastoma-binding protein RBQ-3


Mass: 59179.359 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
#2: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 34390.992 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
#3: Protein Histone-lysine N-methyltransferase 2A / Lysine N-methyltransferase 2A / ALL-1 / CXXC-type zinc finger protein 7 / Myeloid/lymphoid or mixed- ...Lysine N-methyltransferase 2A / ALL-1 / CXXC-type zinc finger protein 7 / Myeloid/lymphoid or mixed-lineage leukemia / Myeloid/lymphoid or mixed-lineage leukemia protein 1 / Trithorax-like protein / Zinc finger protein HRX


Mass: 24141.732 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KMT2A, ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1 / Production host: Escherichia coli (E. coli)
References: UniProt: Q03164, [histone H3]-lysine4 N-trimethyltransferase
#4: Protein Set1/Ash2 histone methyltransferase complex subunit ASH2 / ASH2-like protein


Mass: 60244.641 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
#5: Protein Histone H3


Mass: 15437.144 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
#6: Protein Histone H4


Mass: 11394.426 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
#7: 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, h2ac14, LOC494591, XELAEV_18003602mg / Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8
#8: Protein Histone H2B 1.1 / H2B1.1


Mass: 13655.948 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: P02281

-
DNA chain , 2 types, 2 molecules OP

#9: DNA chain DNA (145-MER)


Mass: 45610.043 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#10: DNA chain DNA (145-MER)


Mass: 45138.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1MLL1 in complex with RbBP5, WDR5, SET1, and ASH2L bound to the nucleosome (Mode01)COMPLEXall0MULTIPLE SOURCES
2RbBP5, WDR5, SET1, and ASH2LCOMPLEX#1-#41RECOMBINANT
3nucleosomeCOMPLEX#5-#101RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Xenopus laevis (African clawed frog)8355
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K

-
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: OTHER
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 53.4 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.15.2_3472: / Classification: refinement
CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionNum. of particles: 30322 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00620743
ELECTRON MICROSCOPYf_angle_d0.83529274
ELECTRON MICROSCOPYf_dihedral_angle_d19.76811432
ELECTRON MICROSCOPYf_chiral_restr0.0523285
ELECTRON MICROSCOPYf_plane_restr0.0072701

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

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. 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.
  • 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 Accession Codes are Changing Soon! / 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.
  • 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

-
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.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

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