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- EMDB-25027: Anaphase Promoting Complex delta APC7 + UBE2C,substrate,UbV,CDH1 -

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Basic information

Entry
Database: EMDB / ID: EMD-25027
TitleAnaphase Promoting Complex delta APC7 + UBE2C,substrate,UbV,CDH1
Map dataanaphase promoting complex / cyclosome lacking APC7 subunit, bound to Ubiquitin variant, substrate, UBE2C
Sample
  • Complex: Anaphase Promoting Complex delta APC7
Function / homology
Function and homology information


negative regulation of mitotic spindle pole body separation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of mitotic actomyosin contractile ring contraction / deactivation of mitotic spindle assembly checkpoint / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / free ubiquitin chain polymerization / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint ...negative regulation of mitotic spindle pole body separation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of mitotic actomyosin contractile ring contraction / deactivation of mitotic spindle assembly checkpoint / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / free ubiquitin chain polymerization / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / protein branched polyubiquitination / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / metaphase/anaphase transition of mitotic cell cycle / positive regulation of synaptic plasticity / (E3-independent) E2 ubiquitin-conjugating enzyme / anaphase-promoting complex binding / Phosphorylation of the APC/C / positive regulation of mitotic metaphase/anaphase transition / ubiquitin ligase activator activity / positive regulation of ubiquitin protein ligase activity / positive regulation of ubiquitin-dependent protein catabolic process / protein K11-linked ubiquitination / positive regulation of dendrite morphogenesis / regulation of mitotic metaphase/anaphase transition / exit from mitosis / ubiquitin-ubiquitin ligase activity / E2 ubiquitin-conjugating enzyme / ubiquitin-like protein ligase binding / Regulation of APC/C activators between G1/S and early anaphase / ubiquitin conjugating enzyme activity / cullin family protein binding / Antigen processing: Ubiquitination & Proteasome degradation / Transcriptional Regulation by VENTX / positive regulation of axon extension / protein K48-linked ubiquitination / ubiquitin ligase complex / regulation of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / cyclin binding / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / CDK-mediated phosphorylation and removal of Cdc6 / kinetochore / spindle / protein polyubiquitination / ubiquitin-protein transferase activity / positive regulation of protein catabolic process / Separation of Sister Chromatids / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / mitotic cell cycle / nervous system development / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / proteasome-mediated ubiquitin-dependent protein catabolic process / molecular adaptor activity / cell differentiation / protein ubiquitination / cell division / negative regulation of gene expression / ubiquitin protein ligase binding / nucleolus / zinc ion binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Anaphase-promoting complex subunit 15 / The WD repeat Cdc20/Fizzy family / Anaphase-promoting complex subunit 15 / Anaphase-promoting complex subunit 1, C-terminal / Anaphase-promoting complex subunit 1, middle domain / : / : / : / Anaphase-promoting complex subunit 1 WD40 beta-propeller domain / Anaphase-promoting complex sub unit 1 C-terminal domain ...Anaphase-promoting complex subunit 15 / The WD repeat Cdc20/Fizzy family / Anaphase-promoting complex subunit 15 / Anaphase-promoting complex subunit 1, C-terminal / Anaphase-promoting complex subunit 1, middle domain / : / : / : / Anaphase-promoting complex subunit 1 WD40 beta-propeller domain / Anaphase-promoting complex sub unit 1 C-terminal domain / Anaphase-promoting complex subunit 1 middle domain / APC1 beta sandwich domain / Anaphase-promoting complex subunit 5, N-terminal domain / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex, subunit 16 / Apc13 / Apc13p protein / Anaphase-promoting complex subunit 1 / Anaphase-promoting complex subunit 5 domain / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex subunit APC10/Doc1 / Anaphase-promoting complex, subunit CDC26 / Anaphase-promoting complex APC subunit CDC26 / Anaphase-promoting complex subunit 11, RING-H2 finger / Anaphase-promoting complex subunit 11 RING-H2 finger / Anaphase-promoting complex subunit 2, C-terminal / Anaphase-promoting complex subunit 2 / Anaphase promoting complex (APC) subunit 2 / Anaphase promoting complex (APC) subunit 2 / APC10/DOC domain / Anaphase-promoting complex, subunit 10 (APC10) / DOC domain profile. / Anaphase-promoting complex, subunit 10 (APC10) / Anaphase-promoting complex subunit 4, WD40 domain / : / : / Anaphase-promoting complex subunit 4 WD40 domain / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Ubiquitin-conjugating enzyme/RWD-like / Tetratricopeptide repeats / Tetratricopeptide repeat / Galactose-binding-like domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Zinc finger, RING/FYVE/PHD-type / Winged helix DNA-binding domain superfamily / 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 / Winged helix-like DNA-binding domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Ubiquitin-conjugating enzyme E2 C / APC/C activator protein CDH1 / Anaphase-promoting complex subunit 15 / Anaphase-promoting complex subunit CDC26 / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex subunit 13 / Anaphase-promoting complex subunit 1 / Anaphase-promoting complex subunit 11 / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex subunit 2 / Anaphase-promoting complex subunit 10
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.6 Å
AuthorsFerguson CJ / Brown NG / Prabu JR / Watson ER / Schulman BA / Bonni A
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)5K08HD099314-02 United States
CitationJournal: Mol Cell / Year: 2022
Title: APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain.
Authors: Cole J Ferguson / Olivia Urso / Tatyana Bodrug / Brandon M Gassaway / Edmond R Watson / Jesuraj R Prabu / Pablo Lara-Gonzalez / Raquel C Martinez-Chacin / Dennis Y Wu / Karlla W Brigatti / ...Authors: Cole J Ferguson / Olivia Urso / Tatyana Bodrug / Brandon M Gassaway / Edmond R Watson / Jesuraj R Prabu / Pablo Lara-Gonzalez / Raquel C Martinez-Chacin / Dennis Y Wu / Karlla W Brigatti / Erik G Puffenberger / Cora M Taylor / Barbara Haas-Givler / Robert N Jinks / Kevin A Strauss / Arshad Desai / Harrison W Gabel / Steven P Gygi / Brenda A Schulman / Nicholas G Brown / Azad Bonni /
Abstract: Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of ...Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of the E3 ubiquitin ligase anaphase promoting complex (APC). In mechanistic studies, we uncover a critical role for APC7 during the recruitment and ubiquitination of APC substrates. In proteomics analyses of the brain from mice harboring the patient-specific APC7 mutation, we identify the chromatin-associated protein Ki-67 as an APC7-dependent substrate of the APC in neurons. Conditional knockout of the APC coactivator protein Cdh1, but not Cdc20, leads to the accumulation of Ki-67 protein in neurons in vivo, suggesting that APC7 is required for the function of Cdh1-APC in the brain. Deregulated neuronal Ki-67 upon APC7 loss localizes predominantly to constitutive heterochromatin. Our findings define an essential function for APC7 and Cdh1-APC in neuronal heterochromatin regulation, with implications for understanding human brain development and disease.
History
DepositionSep 27, 2021-
Header (metadata) releaseJan 12, 2022-
Map releaseJan 12, 2022-
UpdateJan 19, 2022-
Current statusJan 19, 2022Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.019
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.019
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_25027.png

Downloads & links

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Map

FileDownload / File: emd_25027.map.gz / Format: CCP4 / Size: 129.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationanaphase promoting complex / cyclosome lacking APC7 subunit, bound to Ubiquitin variant, substrate, UBE2C
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.34 Å/pix.
x 324 pix.
= 434.16 Å		1.34 Å/pix.
x 324 pix.
= 434.16 Å		1.34 Å/pix.
x 324 pix.
= 434.16 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.34 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.019 / Movie #1: 0.019
Minimum - Maximum-0.005234458 - 0.041231077
Average (Standard dev.)0.0004920546 (±0.0032137241)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions324324324
Spacing324324324
CellA=B=C: 434.16 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.341.341.34
M x/y/z324324324
origin x/y/z0.0000.0000.000
length x/y/z434.160434.160434.160
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS324324324
D min/max/mean-0.0050.0410.000

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Supplemental data

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Half map: #1

Fileemd_25027_half_map_1.map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_25027_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : Anaphase Promoting Complex delta APC7

EntireName: Anaphase Promoting Complex delta APC7
Components
  • Complex: Anaphase Promoting Complex delta APC7

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Supramolecule #1: Anaphase Promoting Complex delta APC7

SupramoleculeName: Anaphase Promoting Complex delta APC7 / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
Molecular weightExperimental: 1.2 MDa

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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
VitrificationCryogen name: NITROGEN

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionResolution.type: BY AUTHOR / Resolution: 7.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 54172
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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