[English] 日本語
Yorodumi
- PDB-8oqi: Cryo-EM structure of the wild-type alpha-synuclein fibril. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8oqi
TitleCryo-EM structure of the wild-type alpha-synuclein fibril.
ComponentsAlpha-synuclein
KeywordsPROTEIN FIBRIL / alpha-synuclein / amyloid / fibril / Parkinson's disease
Function / homology
Function and homology information


negative regulation of mitochondrial electron transport, NADH to ubiquinone / : / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / 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 mitochondrial electron transport, NADH to ubiquinone / : / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / 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 / mitochondrial membrane organization / regulation of synaptic vesicle recycling / negative regulation of chaperone-mediated autophagy / regulation of reactive oxygen species biosynthetic process / negative regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / regulation of glutamate secretion / dopamine biosynthetic process / SNARE complex assembly / regulation of norepinephrine uptake / response to iron(II) ion / positive regulation of neurotransmitter secretion / positive regulation of inositol phosphate biosynthetic process / regulation of locomotion / negative regulation of dopamine metabolic process / regulation of macrophage activation / transporter regulator activity / negative regulation of microtubule polymerization / synaptic vesicle transport / synaptic vesicle priming / dopamine uptake involved in synaptic transmission / protein kinase inhibitor activity / mitochondrial ATP synthesis coupled electron transport / regulation of dopamine secretion / dynein complex binding / positive regulation of receptor recycling / negative regulation of thrombin-activated receptor signaling pathway / cuprous ion binding / nuclear outer membrane / response to magnesium ion / positive regulation of endocytosis / positive regulation of exocytosis / synaptic vesicle exocytosis / kinesin binding / enzyme inhibitor activity / synaptic vesicle endocytosis / cysteine-type endopeptidase inhibitor activity / negative regulation of serotonin uptake / response to type II interferon / regulation of presynapse assembly / alpha-tubulin binding / beta-tubulin binding / behavioral response to cocaine / phospholipase binding / supramolecular fiber organization / phospholipid metabolic process / cellular response to fibroblast growth factor stimulus / inclusion body / axon terminus / Hsp70 protein binding / cellular response to epinephrine stimulus / response to interleukin-1 / regulation of microtubule cytoskeleton organization / cellular response to copper ion / positive regulation of release of sequestered calcium ion into cytosol / SNARE binding / adult locomotory behavior / excitatory postsynaptic potential / phosphoprotein binding / protein tetramerization / microglial cell activation / fatty acid metabolic process / ferrous iron binding / regulation of long-term neuronal synaptic plasticity / synapse organization / protein destabilization / PKR-mediated signaling / phospholipid binding / receptor internalization / tau protein binding / long-term synaptic potentiation / terminal bouton / positive regulation of inflammatory response / synaptic vesicle membrane / actin cytoskeleton / actin binding / growth cone / cellular response to oxidative stress / neuron apoptotic process / cell cortex / histone binding / response to lipopolysaccharide / microtubule binding / molecular adaptor activity / chemical synaptic transmission / amyloid fibril formation / mitochondrial outer membrane / negative regulation of neuron apoptotic process / oxidoreductase activity
Similarity search - Function
Synuclein / Alpha-synuclein / Synuclein
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsPesch, V. / Reithofer, S. / Ma, L. / Flores-Fernandez, J.M. / Oezduezenciler, P. / Busch, Y. / Lien, Y. / Rudtke, O. / Frieg, B. / Schroeder, G.F. ...Pesch, V. / Reithofer, S. / Ma, L. / Flores-Fernandez, J.M. / Oezduezenciler, P. / Busch, Y. / Lien, Y. / Rudtke, O. / Frieg, B. / Schroeder, G.F. / Wille, H. / Tamgueney, G.
Funding support United States, Germany, 2items
OrganizationGrant numberCountry
Michael J. Fox FoundationMJFF-0098 United States
Helmholtz Association Germany
CitationJournal: Brain / Year: 2024
Title: Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease.
Authors: Verena Pesch / José Miguel Flores-Fernandez / Sara Reithofer / Liang Ma / Pelin Özdüzenciler / Yannick Busch / Aishwarya Sriraman / YongLiang Wang / Sara Amidian / Chiara V M Kroepel / ...Authors: Verena Pesch / José Miguel Flores-Fernandez / Sara Reithofer / Liang Ma / Pelin Özdüzenciler / Yannick Busch / Aishwarya Sriraman / YongLiang Wang / Sara Amidian / Chiara V M Kroepel / Laura Müller / Yi Lien / Olivia Rudtke / Benedikt Frieg / Gunnar F Schröder / Holger Wille / Gültekin Tamgüney /
Abstract: The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease ...The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/- mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders.
History
DepositionApr 12, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 13, 2024Provider: repository / Type: Initial release
Revision 1.1May 15, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-synuclein
B: Alpha-synuclein
C: Alpha-synuclein
D: Alpha-synuclein
E: Alpha-synuclein
F: Alpha-synuclein
G: Alpha-synuclein
H: Alpha-synuclein
I: Alpha-synuclein
J: Alpha-synuclein


Theoretical massNumber of molelcules
Total (without water)144,76110
Polymers144,76110
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1chain "A"
d_2ens_1chain "B"
d_3ens_1chain "C"
d_4ens_1chain "D"
d_5ens_1chain "E"
d_6ens_1chain "F"
d_7ens_1chain "G"
d_8ens_1chain "H"
d_9ens_1chain "I"
d_10ens_1chain "J"

NCS domain segments:

Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: TYR / Beg label comp-ID: TYR / End auth comp-ID: PHE / End label comp-ID: PHE / Auth seq-ID: 39 - 94 / Label seq-ID: 39 - 94

Dom-IDAuth asym-IDLabel asym-ID
d_1AA
d_2BB
d_3CC
d_4DD
d_5EE
d_6FF
d_7GG
d_8HH
d_9II
d_10JJ

NCS oper:
IDCodeMatrixVector
1given(-0.999977677497, -0.00668165454656, -5.62849764392E-7), (0.00668165454668, -0.999977677497, -2.13326670996E-7), (-5.61411825055E-7, -2.17082676698E-7, 1)265.882471825, 264.11171345, 2.41009282691
2given(0.999910690911, 0.0133645127859, 6.4676325693E-7), (-0.0133645127861, 0.999910690911, 3.09458445897E-7), (-6.42569733736E-7, -3.18074484262E-7, 1)-1.75903992619, 1.78261234224, 4.82011482535
3given(-0.999799090767, -0.0200444032475, -3.05348574424E-7), (0.0200444032476, -0.999799090767, -1.53338411269E-7), (-3.02213650127E-7, -1.59428134123E-7, 1)267.629328902, 262.317484291, 7.23005521638
4given(0.999642848698, 0.0267240537246, 2.61142270104E-7), (-0.0267240537246, 0.999642848698, -5.41057996486E-9), (-2.61193595431E-7, -1.57013248684E-9, 1)-3.4937054614, 3.58827903434, 9.64003093305
5given(-0.999441932354, -0.0334039496667, -3.56636455179E-7), (0.0334039496668, -0.999441932354, -1.68178096599E-7), (-3.50819615238E-7, -1.79997308043E-7, 1)269.352140043, 260.500047529, 12.0500634719
6given(0.999196421546, 0.0400813069954, 2.31604063537E-7), (-0.0400813069954, 0.999196421546, 1.68238442329E-8), (-2.30743629836E-7, -2.60933185262E-8, 1)-5.20434510708, 5.41722148086, 14.4600303719
7given(-0.998906319755, -0.0467564365014, -2.79586581782E-8), (0.0467564365014, -0.998906319755, 1.14224783105E-7), (-3.32688241642E-8, 1.12792610491E-7, 1)271.050327488, 258.659811318, 16.8699900139
8given(0.998571501207, 0.0534317974369, 5.28131209778E-7), (-0.0534317974371, 0.998571501207, 3.76369752301E-7), (-5.07266662616E-7, -4.04051108385E-7, 1)-6.89049041568, 7.26890954537, 19.2801094982
9given(-0.998192226534, -0.0601022369574, -6.12794325452E-7), (0.0601022369577, -0.998192226534, -4.46010244537E-7), (-5.84880318727E-7, -4.82034268806E-7, 1)272.724098091, 256.796967462, 21.6901282437

-
Components

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


Mass: 14476.108 Da / Num. of mol.: 10
Source method: isolated from a genetically manipulated source
Details: N-terminally acetylated human wild-type alpha-synuclein.
Source: (gene. exp.) Homo sapiens (human) / Gene: SNCA, NACP, PARK1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P37840

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Human wild-type alpha-synuclein fibril / Type: COMPLEX
Details: N-terminally acetylated human wild-type alpha-synuclein
Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli BL21(DE3) (bacteria)
Buffer solutionpH: 7.2
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: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 30 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

Software
NameVersionClassificationNB
phenix.real_space_refine1.19.2_4158refinement
PHENIX1.19.2_4158refinement
CTF correctionType: NONE
Helical symmertyAngular rotation/subunit: 179.62 ° / Axial rise/subunit: 2.41 Å / Axial symmetry: C1
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 27610
Details: The alpha-synuclein fibril was reconstructed using RELION-3.1.
Symmetry type: HELICAL
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 56.31 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.01313830
ELECTRON MICROSCOPYf_angle_d2.0085190
ELECTRON MICROSCOPYf_chiral_restr0.1147680
ELECTRON MICROSCOPYf_plane_restr0.0068650
ELECTRON MICROSCOPYf_dihedral_angle_d18.28631260
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AELECTRON MICROSCOPYNCS constraints0.000582599456592
ens_1d_3AELECTRON MICROSCOPYNCS constraints0.000563242468017
ens_1d_4AELECTRON MICROSCOPYNCS constraints0.000579861558612
ens_1d_5AELECTRON MICROSCOPYNCS constraints0.000564553631986
ens_1d_6AELECTRON MICROSCOPYNCS constraints0.000408143770637
ens_1d_7AELECTRON MICROSCOPYNCS constraints0.000573924979394
ens_1d_8AELECTRON MICROSCOPYNCS constraints0.000578506874847
ens_1d_9AELECTRON MICROSCOPYNCS constraints0.00056769526007
ens_1d_10AELECTRON MICROSCOPYNCS constraints0.000594551183008

+
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