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- EMDB-39095: Funes-induced Orb2 amyloid like endogenous Orb2 amyloid -

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Basic information

Entry
Database: EMDB / ID: EMD-39095
TitleFunes-induced Orb2 amyloid like endogenous Orb2 amyloid
Map data
Sample
  • Complex: Funes-induced Orb2 amyloid filament
    • Protein or peptide: Translational regulator orb2
KeywordsTranslator regulator / chaperone / PROTEIN FIBRIL
Function / homology
Function and homology information


dendrite terminus / sperm axoneme assembly / asymmetric cell division / sperm individualization / male courtship behavior / translation activator activity / translation factor activity, RNA binding / male meiosis I / long-term memory / negative regulation of cytoplasmic translation ...dendrite terminus / sperm axoneme assembly / asymmetric cell division / sperm individualization / male courtship behavior / translation activator activity / translation factor activity, RNA binding / male meiosis I / long-term memory / negative regulation of cytoplasmic translation / axon terminus / mRNA regulatory element binding translation repressor activity / synaptic membrane / positive regulation of translation / mRNA 3'-UTR binding / presynapse / ribosome binding / cell body / cell cortex / spermatogenesis / perikaryon / neuron projection / negative regulation of translation / protein stabilization / postsynapse / axon / synapse / perinuclear region of cytoplasm / protein-containing complex / RNA binding / identical protein binding / nucleus / 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
Translational regulator orb2
Similarity search - Component
Biological speciesDrosophila melanogaster (fruit fly)
Methodhelical reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsHervas R / Si K
Funding support United States, Hong Kong, 2 items
OrganizationGrant numberCountry
Other private United States
Other government Hong Kong
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: A J-domain protein enhances memory by promoting physiological amyloid formation in .
Authors: Kyle Patton / Yangyang Yi / Raj Burt / Kevin Kan-Shing Ng / Mayur Mukhi / Peerzada Shariq Shaheen Khaki / Ruben Hervas / Kausik Si /
Abstract: Memory requires experience-dependent alterations in the synaptic proteome. Chaperones interface between the environment and the proteome. Manipulating J-domain protein (JDP) chaperones, the most ...Memory requires experience-dependent alterations in the synaptic proteome. Chaperones interface between the environment and the proteome. Manipulating J-domain protein (JDP) chaperones, the most diverse family of chaperones, in a neuronal circuit that encodes associative long-term memories, we identified yet uncharacterized JDPs that transduce sensory cues. One of these JDPs, CG10375, which we named Funes, enhances memory when overexpressed and impairs memory when functionally impaired. Funes overexpression enhances memory formation even when sensory stimuli are suboptimal. At the circuit level, Funes acts on neurons where conditioned and unconditioned stimuli converge to form associative memories. From a proteomic-based screen, we found that overexpression of Funes changes the solubility of a small subset of proteins, one of which is the mRNA-binding protein Orb2. Combining in vitro and in vivo biophysical, biochemical, and cryo-EM structural analyses, we found that Funes associates with oligomeric Orb2 and promotes the formation of translationally active amyloids. Perturbation of the conserved J domain eliminates the ability of Funes to facilitate amyloid assembly and promote memory. We posit that the brain harbors chaperones that influence memory by regulating physiological amyloid formation.
History
DepositionFeb 8, 2024-
Header (metadata) releaseSep 3, 2025-
Map releaseSep 3, 2025-
UpdateMar 18, 2026-
Current statusMar 18, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_39095.png

Downloads & links

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Map

FileDownload / File: emd_39095.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 220 pix.
= 238.48 Å		1.08 Å/pix.
x 220 pix.
= 238.48 Å		1.08 Å/pix.
x 220 pix.
= 238.48 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.084 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0124
Minimum - Maximum-0.036233496 - 0.052395366
Average (Standard dev.)0.00020234015 (±0.0033360315)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions220220220
Spacing220220220
CellA=B=C: 238.48 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_39095_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: #1

Fileemd_39095_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : Funes-induced Orb2 amyloid filament

EntireName: Funes-induced Orb2 amyloid filament
Components
  • Complex: Funes-induced Orb2 amyloid filament
    • Protein or peptide: Translational regulator orb2

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Supramolecule #1: Funes-induced Orb2 amyloid filament

SupramoleculeName: Funes-induced Orb2 amyloid filament / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Drosophila melanogaster (fruit fly)

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Macromolecule #1: Translational regulator orb2

MacromoleculeName: Translational regulator orb2 / type: protein_or_peptide / ID: 1 / Number of copies: 9 / Enantiomer: LEVO
Source (natural)Organism: Drosophila melanogaster (fruit fly)
Molecular weightTheoretical: 3.97417 KDa
SequenceString:
QLHQQQHQQQ HQQHQQHQQQ QQLHQHQQQL S

UniProtKB: Translational regulator orb2

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

Concentration0.25 mg/mL
BufferpH: 7.15
Details: 10 mM HEPES pH7.15, 75 mM NaCl, 10 mM KCl, 2mM MgCl2 and 5 mM TCEP
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV
DetailsOrb2 amyloid induced by the JDP Funes from oligomeric Orb2 isolte from fly heads

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 49.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.6 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.82 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.42 °
Applied symmetry - Helical parameters - Axial symmetry: C3 (3 fold cyclic)
Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 7807
CTF correctionSoftware - Name: Gctf / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: EMDB MAP
EMDB ID:

39095

Final angle assignmentType: NOT APPLICABLE

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