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- EMDB-27243: Cryo-EM map of MORF-WHs in complex with 197bp nucleosome aided by scFv -

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Basic information

Entry
Database: EMDB / ID: EMD-27243
TitleCryo-EM map of MORF-WHs in complex with 197bp nucleosome aided by scFv
Map dataMain map
Sample
  • Complex: MORF-WH and Nucleosome complex
Keywordsnucleosome / single-chain antibody fragment / charge-charge interaction / MORF / NUCLEAR PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.0 Å
AuthorsZhou BR
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)Intramural Research Program United States
CitationJournal: Nat Commun / Year: 2023
Title: MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.
Authors: Dustin C Becht / Brianna J Klein / Akinori Kanai / Suk Min Jang / Khan L Cox / Bing-Rui Zhou / Sabrina K Phanor / Yi Zhang / Ruo-Wen Chen / Christopher C Ebmeier / Catherine Lachance / ...Authors: Dustin C Becht / Brianna J Klein / Akinori Kanai / Suk Min Jang / Khan L Cox / Bing-Rui Zhou / Sabrina K Phanor / Yi Zhang / Ruo-Wen Chen / Christopher C Ebmeier / Catherine Lachance / Maxime Galloy / Amelie Fradet-Turcotte / Martha L Bulyk / Yawen Bai / Michael G Poirier / Jacques Côté / Akihiko Yokoyama / Tatiana G Kutateladze /
Abstract: Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the ...Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.
History
DepositionJun 7, 2022-
Header (metadata) releaseFeb 1, 2023-
Map releaseFeb 1, 2023-
UpdateAug 30, 2023-
Current statusAug 30, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27243.png

Downloads & links

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Map

FileDownload / File: emd_27243.map.gz / Format: CCP4 / Size: 3.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMain map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.91 Å/pix.
x 96 pix.
= 279.648 Å		2.91 Å/pix.
x 96 pix.
= 279.648 Å		2.91 Å/pix.
x 96 pix.
= 279.648 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.913 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum-0.4336991 - 1.478561
Average (Standard dev.)0.0022760245 (±0.089869626)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions969696
Spacing969696
CellA=B=C: 279.648 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_27243_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_27243_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_27243_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : MORF-WH and Nucleosome complex

EntireName: MORF-WH and Nucleosome complex
Components
  • Complex: MORF-WH and Nucleosome complex

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Supramolecule #1: MORF-WH and Nucleosome complex

SupramoleculeName: MORF-WH and Nucleosome complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionNumber classes used: 1 / Resolution.type: BY AUTHOR / Resolution: 7.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3) / Number images used: 4629
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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