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- EMDB-38198: hCDCA7 bound to nucleosome with hemimethylated CpG in 3'-linker DNA -

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Basic information

Entry
Database: EMDB / ID: EMD-38198
TitlehCDCA7 bound to nucleosome with hemimethylated CpG in 3'-linker DNA
Map data
Sample
  • Complex: hCDCA7 bound to nucleosome
    • Complex: Histone H3.1
    • Complex: Histone H4
    • Complex: Histone H2A
    • Complex: Histone H2B
    • Complex: CDCA7
    • Complex: DNA (157-mer)
KeywordsDNA methylation maintenance / hemimethylated DNA / DNA BINDING PROTEIN
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.18 Å
AuthorsHiruta M / Shikimachi R / Kikuchi A / Nishiyama A / Funabiki H / Arita K
Funding support Japan, 1 items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)JP19H05741 Japan
CitationJournal: Sci Adv / Year: 2024
Title: CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.
Authors: Isabel E Wassing / Atsuya Nishiyama / Reia Shikimachi / Qingyuan Jia / Amika Kikuchi / Moeri Hiruta / Keita Sugimura / Xin Hong / Yoshie Chiba / Junhui Peng / Christopher Jenness / Makoto ...Authors: Isabel E Wassing / Atsuya Nishiyama / Reia Shikimachi / Qingyuan Jia / Amika Kikuchi / Moeri Hiruta / Keita Sugimura / Xin Hong / Yoshie Chiba / Junhui Peng / Christopher Jenness / Makoto Nakanishi / Li Zhao / Kyohei Arita / Hironori Funabiki /
Abstract: Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at ...Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-electron microscopy structural analysis of the CDCA7-nucleosome complex reveals that the HMZF domain can recognize hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle, whereas UHRF1, the critical activator of the maintenance methyltransferase DNMT1, cannot. CDCA7 recruits HELLS to hemimethylated chromatin and facilitates UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and DNMT1.
History
DepositionDec 3, 2023-
Header (metadata) releaseDec 4, 2024-
Map releaseDec 4, 2024-
UpdateMar 12, 2025-
Current statusMar 12, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_38198.png

Downloads & links

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Map

FileDownload / File: emd_38198.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
1.2 Å/pix.
x 250 pix.
= 300. Å		1.2 Å/pix.
x 250 pix.
= 300. Å		1.2 Å/pix.
x 250 pix.
= 300. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.2 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.5863367 - 0.99375427
Average (Standard dev.)-0.000008293354 (±0.022746215)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions250250250
Spacing250250250
CellA=B=C: 300.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_38198_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_38198_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : hCDCA7 bound to nucleosome

EntireName: hCDCA7 bound to nucleosome
Components
  • Complex: hCDCA7 bound to nucleosome
    • Complex: Histone H3.1
    • Complex: Histone H4
    • Complex: Histone H2A
    • Complex: Histone H2B
    • Complex: CDCA7
    • Complex: DNA (157-mer)

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Supramolecule #1: hCDCA7 bound to nucleosome

SupramoleculeName: hCDCA7 bound to nucleosome / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #2: Histone H3.1

SupramoleculeName: Histone H3.1 / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Histone H4

SupramoleculeName: Histone H4 / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: Histone H2A

SupramoleculeName: Histone H2A / type: complex / ID: 4 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #5: Histone H2B

SupramoleculeName: Histone H2B / type: complex / ID: 5 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #6: CDCA7

SupramoleculeName: CDCA7 / type: complex / ID: 6 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #7: DNA (157-mer)

SupramoleculeName: DNA (157-mer) / type: complex / ID: 7 / Parent: 1
Source (natural)Organism: synthetic construct (others) / Synthetically produced: Yes

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.725 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.18 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 154998
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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