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- EMDB-61134: Cryo-EM structure of P25alpha full-length A119V fibril -

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Basic information

Entry
Database: EMDB / ID: EMD-61134
TitleCryo-EM structure of P25alpha full-length A119V fibril
Map data
Sample
  • Organelle or cellular component: Cryo-EM structure of P25alpha core fibril
    • Protein or peptide: Tubulin polymerization-promoting protein
KeywordsPROTEIN FIBRIL / amyloid / CYTOSOLIC PROTEIN
Function / homology
Function and homology information


microtubule nucleation by microtubule organizing center / postsynaptic Golgi apparatus / myelin assembly / negative regulation of tubulin deacetylation / positive regulation of myelination / astral microtubule organization / microtubule bundle formation / oligodendrocyte development / positive regulation of protein polymerization / oligodendrocyte differentiation ...microtubule nucleation by microtubule organizing center / postsynaptic Golgi apparatus / myelin assembly / negative regulation of tubulin deacetylation / positive regulation of myelination / astral microtubule organization / microtubule bundle formation / oligodendrocyte development / positive regulation of protein polymerization / oligodendrocyte differentiation / microtubule polymerization / microtubule organizing center / regulation of microtubule cytoskeleton organization / positive regulation of protein-containing complex assembly / tubulin binding / mitotic spindle / microtubule binding / microtubule / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / cell division / GTPase activity / perinuclear region of cytoplasm / magnesium ion binding / protein homodimerization activity / mitochondrion / nucleus / cytoplasm / cytosol
Similarity search - Function
P25-alpha / p25-alpha / EF-hand domain pair
Similarity search - Domain/homology
Tubulin polymerization-promoting protein
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 2.49 Å
AuthorsXia WC / Sun YP / Huang CA / Liu C
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell / Year: 2026
Title: TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy.
Authors: Shuyi Zeng / Shenqing Zhang / Shengnan Zhang / Yun Fan / Wencheng Xia / Feiyang Chen / Chengan Huang / Shiran Lv / Jinxia Lu / Yunpeng Sun / Kaien Liu / Yunxia Li / Yaoyang Zhang / Jian Wang ...Authors: Shuyi Zeng / Shenqing Zhang / Shengnan Zhang / Yun Fan / Wencheng Xia / Feiyang Chen / Chengan Huang / Shiran Lv / Jinxia Lu / Yunpeng Sun / Kaien Liu / Yunxia Li / Yaoyang Zhang / Jian Wang / Cong Liu / Dan Li /
Abstract: Detection of α-synuclein (α-syn) amyloid seeds in human biofluids has attracted great interest for clinical diagnosis of synucleinopathies. However, as a common biomarker, α-syn lacks specificity ...Detection of α-synuclein (α-syn) amyloid seeds in human biofluids has attracted great interest for clinical diagnosis of synucleinopathies. However, as a common biomarker, α-syn lacks specificity in reliably differentiating distinct disorders. Here, we report tubulin polymerization promoting protein (TPPP/p25) as a cerebrospinal fluid (CSF) biomarker for the specific diagnosis of multiple system atrophy (MSA). We demonstrate that native TPPP/p25 is self-protected against amyloid aggregation, while disease-related mutation disrupts this protection, triggering TPPP/p25 aggregation. Cryo-electron microscopy (cryo-EM) analysis reveals that the well-folded core domain (CORE) undergoes large conformational changes to mediate amyloid formation. Based on this insight, we developed a seed amplification assay using a minimized CORE (miniCORE) monomer, which detects TPPP/p25 amyloid seeds in CSF and robustly differentiates MSA from Parkinson's disease (PD) and other neurodegenerative diseases. Our findings establish misfolded TPPP/p25 as a promising, specific biomarker in biofluids for MSA diagnosis.
History
DepositionAug 9, 2024-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateJun 3, 2026-
Current statusJun 3, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_61134.png

Downloads & links

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Map

FileDownload / File: emd_61134.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 360 pix.
= 298.8 Å		0.83 Å/pix.
x 360 pix.
= 298.8 Å		0.83 Å/pix.
x 360 pix.
= 298.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.007
Minimum - Maximum-0.03653545 - 0.07799928
Average (Standard dev.)0.00023901548 (±0.0021902479)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 298.8 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_61134_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_61134_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : Cryo-EM structure of P25alpha core fibril

EntireName: Cryo-EM structure of P25alpha core fibril
Components
  • Organelle or cellular component: Cryo-EM structure of P25alpha core fibril
    • Protein or peptide: Tubulin polymerization-promoting protein

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Supramolecule #1: Cryo-EM structure of P25alpha core fibril

SupramoleculeName: Cryo-EM structure of P25alpha core fibril / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Tubulin polymerization-promoting protein

MacromoleculeName: Tubulin polymerization-promoting protein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.767877 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MADKAKPAKA ANRTPPKSPG DPSKDRAAKR LSLESEGAGE GAAASPELSA LEEAFRRFAV HGDARATGRE MHGKNWSKLC KDCQVIDGR NVTVTDVDIV FSKIKGKSCR TITFEQFQEV LEELAKKRFK DKSSEEAVRE VHRLIEGKAP IISGVTKAIS S PTVSRLTD ...String:
MADKAKPAKA ANRTPPKSPG DPSKDRAAKR LSLESEGAGE GAAASPELSA LEEAFRRFAV HGDARATGRE MHGKNWSKLC KDCQVIDGR NVTVTDVDIV FSKIKGKSCR TITFEQFQEV LEELAKKRFK DKSSEEAVRE VHRLIEGKAP IISGVTKAIS S PTVSRLTD TTKFTGSHKE RFDPSGKGKG KAGRVDLVDE SGYVSGYKHA GTYDQKVQGG K

UniProtKB: Tubulin polymerization-promoting protein

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 8.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 2.41 Å
Applied symmetry - Helical parameters - Δ&Phi: 179.40 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 2.49 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 208173
CTF correctionType: NONE
Startup modelType of model: NONE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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