[English] 日本語
Yorodumi
- PDB-9k24: Cryo-EM structure of alpha-synuclein Mini P fibril -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9k24
TitleCryo-EM structure of alpha-synuclein Mini P fibril
ComponentsAlpha-synuclein
KeywordsPROTEIN FIBRIL / amyloid
Function / homology
Function and homology information


neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / mitochondrial membrane organization / regulation of glutamate secretion / PKR-mediated signaling / regulation of macrophage activation / positive regulation of neurotransmitter secretion / regulation of neurotransmitter secretion / platelet alpha granule membrane / regulation of locomotion ...neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / mitochondrial membrane organization / regulation of glutamate secretion / PKR-mediated signaling / regulation of macrophage activation / positive regulation of neurotransmitter secretion / regulation of neurotransmitter secretion / platelet alpha granule membrane / regulation of locomotion / membrane organization / mitochondrial ATP synthesis coupled electron transport / regulation of reactive oxygen species metabolic process / arachidonate binding / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / response to desipramine / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / negative regulation of chaperone-mediated autophagy / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / dopamine biosynthetic process / dopamine metabolic process / negative regulation of dopamine metabolic process / response to iron(II) ion / negative regulation of platelet-derived growth factor receptor signaling pathway / SNARE complex assembly / negative regulation of thrombin-activated receptor signaling pathway / negative regulation of microtubule polymerization / synaptic vesicle priming / synaptic vesicle transport / Lewy body / synaptic vesicle exocytosis / regulation of norepinephrine uptake / transporter regulator activity / phospholipid metabolic process / positive regulation of inositol phosphate biosynthetic process / regulation of dopamine secretion / positive regulation of receptor recycling / regulation of neuronal synaptic plasticity / cuprous ion binding / positive regulation of exocytosis / nuclear outer membrane / dynein complex binding / protein complex oligomerization / synaptic transmission, dopaminergic / response to magnesium ion / positive regulation of endocytosis / neuron apoptotic process / negative regulation of serotonin uptake / positive regulation of synaptic transmission / cysteine-type endopeptidase inhibitor activity / kinesin binding / regulation of presynapse assembly / adult locomotory behavior / synaptic vesicle endocytosis / alpha-tubulin binding / regulation of long-term neuronal synaptic plasticity / beta-tubulin binding / behavioral response to cocaine / phospholipase binding / cellular response to fibroblast growth factor stimulus / response to type II interferon / inclusion body / fatty acid metabolic process / response to interleukin-1 / Hsp70 protein binding / cytoplasmic vesicle membrane / positive regulation of release of sequestered calcium ion into cytosol / excitatory postsynaptic potential / cellular response to copper ion / axon terminus / enzyme inhibitor activity / glutathione metabolic process / SNARE binding / protein tetramerization / protein sequestering activity / regulation of microtubule cytoskeleton organization / long-term synaptic potentiation / receptor internalization / phosphoprotein binding / microglial cell activation / protein destabilization / tubulin binding / ferrous iron binding / synapse organization / phospholipid binding / tau protein binding / enzyme activator activity / positive regulation of inflammatory response / terminal bouton / actin cytoskeleton / synaptic vesicle membrane / negative regulation of neuron apoptotic process / synaptic vesicle / presynapse / response to lipopolysaccharide / growth cone
Similarity search - Function
Synuclein / Alpha-synuclein / Synuclein
Similarity search - Domain/homology
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsXia, W.C. / Liu, C.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Neuron / Year: 2025
Title: Fibril fuzzy coat is important for α-synuclein pathological transmission activity.
Authors: Yuliang Han / Juan Li / Wencheng Xia / Qintong Li / Zihan Sun / Wen Zeng / Yingxin Hu / Kelvin C Luk / Cong Liu / ShengQi Xiang / Zhuohao He /
Abstract: α-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using α-synuclein preformed fibrils as pathological seeds, we observed a ...α-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using α-synuclein preformed fibrils as pathological seeds, we observed a gradual decline in neuronal transmission activity during serial propagation. Fibril polymorphisms were identified from the initial generation: mini-P, with higher neuronal seeding activity, and mini-S, which accelerated recombinant α-synuclein aggregation. Changes in their proportions during propagation explained the overall decline in transmission activity. Cryoelectron microscopy and solid-state nuclear magnetic resonance revealed that both fibrils shared similar core regions but differed in their fuzzy coat flexibilities. The interaction between the fuzzy coat and fibril core substantially influenced neuronal transmission, a model further supported by hydrogen/deuterium exchange mass spectrometry. A mini-P-selective antibody identified active fibril types in newly propagated brain regions in human synucleinopathies. This study highlights the fuzzy coat's pivotal role in pathological protein transmission and suggests it as a potential therapeutic target for synucleinopathies.
History
DepositionOct 17, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 23, 2025Provider: repository / Type: Initial release
Revision 1.1Jun 18, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Alpha-synuclein
A: Alpha-synuclein
C: Alpha-synuclein
E: Alpha-synuclein
D: Alpha-synuclein
F: Alpha-synuclein


Theoretical massNumber of molelcules
Total (without water)87,0076
Polymers87,0076
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Alpha-synuclein / Non-A beta component of AD amyloid / Non-A4 component of amyloid precursor / NACP


Mass: 14501.185 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Snca, Syn / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: O55042
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

-
Sample preparation

ComponentName: Cryo-EM structure of alpha-synuclein Mini P fibril / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: NATURAL
Molecular weightExperimental value: NO
Source (natural)Organism: Mus musculus (house mouse)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 55 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
Helical symmertyAngular rotation/subunit: 179.59 ° / Axial rise/subunit: 2.4 Å / Axial symmetry: C1
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 43228 / Symmetry type: HELICAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0022694
ELECTRON MICROSCOPYf_angle_d0.5893636
ELECTRON MICROSCOPYf_dihedral_angle_d17.48930
ELECTRON MICROSCOPYf_chiral_restr0.053474
ELECTRON MICROSCOPYf_plane_restr0.002450

+
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