[English] 日本語
Yorodumi
- EMDB-40677: Structural insights into cellular control of the human CPEB3 prio... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-40677
TitleStructural insights into cellular control of the human CPEB3 prion, functionally regulated by a labile-amyloid-forming segment
Map data
Sample
  • Complex: Helical assembly of CPEB3 prion-like domain 1
    • Protein or peptide: Cytoplasmic polyadenylation element-binding protein 3
Keywordsprion / amyloid / reversible / helical / PROTEIN FIBRIL
Function / homology
Function and homology information


negative regulation of cytoplasmic translational elongation / CCR4-NOT complex / regulation of dendritic spine development / 3'-UTR-mediated mRNA destabilization / translation factor activity, RNA binding / apical dendrite / mRNA 3'-UTR AU-rich region binding / positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / positive regulation of dendritic spine development ...negative regulation of cytoplasmic translational elongation / CCR4-NOT complex / regulation of dendritic spine development / 3'-UTR-mediated mRNA destabilization / translation factor activity, RNA binding / apical dendrite / mRNA 3'-UTR AU-rich region binding / positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / positive regulation of dendritic spine development / regulation of postsynapse assembly / long-term memory / negative regulation of cytoplasmic translation / mRNA regulatory element binding translation repressor activity / positive regulation of translation / mRNA 3'-UTR binding / cellular response to amino acid stimulus / regulation of synaptic plasticity / RNA stem-loop binding / ribosome binding / midbody / neuron projection / negative regulation of translation / postsynaptic density / synapse / dendrite / negative regulation of transcription by RNA polymerase II / RNA binding / nucleoplasm / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Cytoplasmic polyadenylation element-binding protein, ZZ domain / Cytoplasmic polyadenylation element-binding protein / CEBP, ZZ domain superfamily / Cytoplasmic polyadenylation element-binding protein ZZ domain / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Nucleotide-binding alpha-beta plait domain superfamily
Similarity search - Domain/homology
Cytoplasmic polyadenylation element-binding protein 3
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsFlores MD / Sawaya MR / Boyer DR / Zink S / Fioriti L / Rodriguez JA
Funding support United States, 6 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM128867 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM1295410 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM007185 United States
National Science Foundation (NSF, United States)DMR-1548924 United States
The Pew Charitable TrustsJAR United States
David and Lucile Packard FoundationJAR United States
CitationJournal: Structure / Year: 2025
Title: Structural insights into functional regulation of the human CPEB3 prion by an amyloid-forming segment.
Authors: Maria D Flores / Michael R Sawaya / David R Boyer / Samantha Zink / Susanna Tovmasyan / Adrian Saucedo / Logan S Richards / Chih-Te Zee / Jorge Cardenas / Luana Fioriti / Jose A Rodriguez /
Abstract: The cytoplasmic polyadenylation-element-binding-protein-3 (CPEB3) is a functional prion thought to modulate protein synthesis and enable consolidation of long-term memory in neurons. We report a ...The cytoplasmic polyadenylation-element-binding-protein-3 (CPEB3) is a functional prion thought to modulate protein synthesis and enable consolidation of long-term memory in neurons. We report a cryoelectron microscopy (cryo-EM) structure of amyloid fibrils grown in vitro from the first prion-like domain of human CPEB3 (hCPEB3), revealing their ordered 49-residue core, spanning L103 to F151. CPEB3 lacking that segment coalesces into abnormal puncta in cells compared to wild-type CPEB3, localizes away from dormant p-bodies and toward stress granules, and lacks the ability to influence protein synthesis in neurons. Fluorescence-guided cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) applied to neuronal cells expressing CPEB3 reveal CPEB3-GFP signal from lamellae enriched in multivesicular bodies (MVBs), cavernous multilamellar compartments, and bundled filaments, suggesting a state of induced cellular stress. Accordingly, cells expressing wild-type CPEB3 are less viable than those expressing CPEB3 without its amyloid core, suggesting human CPEB3 regulation may be required to overcome the liability associated with its self-assembly in cells.
History
DepositionMay 2, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateMar 11, 2026-
Current statusMar 11, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_40677.png

Downloads & links

-
Map

FileDownload / File: emd_40677.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 384 pix.
= 330.24 Å		0.86 Å/pix.
x 384 pix.
= 330.24 Å		0.86 Å/pix.
x 384 pix.
= 330.24 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.86 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0278
Minimum - Maximum-0.02719959 - 0.054891244
Average (Standard dev.)0.0001902964 (±0.0018641136)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-192-192-192
Dimensions384384384
Spacing384384384
CellA=B=C: 330.24 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_40677_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_40677_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Helical assembly of CPEB3 prion-like domain 1

EntireName: Helical assembly of CPEB3 prion-like domain 1
Components
  • Complex: Helical assembly of CPEB3 prion-like domain 1
    • Protein or peptide: Cytoplasmic polyadenylation element-binding protein 3

-
Supramolecule #1: Helical assembly of CPEB3 prion-like domain 1

SupramoleculeName: Helical assembly of CPEB3 prion-like domain 1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Truncated CPEB3 prion-like domain generated recombinantly
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23 kDa/nm

-
Macromolecule #1: Cytoplasmic polyadenylation element-binding protein 3

MacromoleculeName: Cytoplasmic polyadenylation element-binding protein 3 / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 5.279761 KDa
Recombinant expressionOrganism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
SequenceString:
LSPSFGSTWS TGTTNAVEDS FFQGITPVNG TMLFQNFPHH VNPVFGGTF

UniProtKB: Cytoplasmic polyadenylation element-binding protein 3

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

BufferpH: 5
Component:
ConcentrationFormulaName
125.0 mMNaClsodium chloride
50.0 mMTris-Base
10.0 mMHK2PO4dipotassium phosphate
5.0 mMglutamic acid
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 200
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK I

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Average electron dose: 52.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.81 Å
Applied symmetry - Helical parameters - Δ&Phi: -3.32 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3) / Number images used: 40329
CTF correctionSoftware - Name: RELION (ver. 3) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: ab initio model
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

+
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://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