[English] 日本語
Yorodumi
- PDB-4rik: Amyloid forming segment, AVVTGVTAV, from the NAC domain of Parkin... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4rik
TitleAmyloid forming segment, AVVTGVTAV, from the NAC domain of Parkinson's disease protein alpha-synuclein, residues 69-77
ComponentsAlpha-synuclein
KeywordsLIPID BINDING PROTEIN / Amyloid / alpha-synuclein / Parkinson's Disease / Toxic Core / NAC
Function / homology
Function and homology information


negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / negative regulation of transporter activity / negative regulation of chaperone-mediated autophagy / mitochondrial membrane organization / regulation of reactive oxygen species biosynthetic process / positive regulation of protein localization to cell periphery / regulation of synaptic vesicle recycling / negative regulation of platelet-derived growth factor receptor signaling pathway / negative regulation of exocytosis / regulation of glutamate secretion / response to iron(II) ion / regulation of norepinephrine uptake / dopamine biosynthetic process / SNARE complex assembly / positive regulation of neurotransmitter secretion / synaptic vesicle priming / dopamine uptake involved in synaptic transmission / regulation of macrophage activation / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / mitochondrial ATP synthesis coupled electron transport / negative regulation of microtubule polymerization / synaptic vesicle transport / dynein complex binding / positive regulation of receptor recycling / regulation of dopamine secretion / positive regulation of endocytosis / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / cuprous ion binding / positive regulation of exocytosis / synaptic vesicle exocytosis / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / kinesin binding / alpha-tubulin binding / regulation of presynapse assembly / synaptic vesicle endocytosis / negative regulation of serotonin uptake / localization / phospholipid metabolic process / supramolecular fiber organization / axon terminus / inclusion body / cellular response to copper ion / Hsp70 protein binding / cellular response to epinephrine stimulus / excitatory postsynaptic potential / response to interleukin-1 / adult locomotory behavior / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / fatty acid metabolic process / long-term synaptic potentiation / regulation of transmembrane transporter activity / ferrous iron binding / synapse organization / phospholipid binding / protein tetramerization / phosphoprotein binding / microglial cell activation / regulation of long-term neuronal synaptic plasticity / negative regulation of protein kinase activity / tau protein binding / protein destabilization / PKR-mediated signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of protein serine/threonine kinase activity / receptor internalization / synaptic vesicle membrane / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / actin cytoskeleton / positive regulation of peptidyl-serine phosphorylation / cellular response to oxidative stress / actin binding / cell cortex / histone binding / growth cone / chemical synaptic transmission / postsynapse / neuron apoptotic process / negative regulation of neuron apoptotic process / amyloid fibril formation / response to lipopolysaccharide / lysosome / molecular adaptor activity / oxidoreductase activity / transcription cis-regulatory region binding
Similarity search - Function
Synuclein / Alpha-synuclein / Synuclein
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.854 Å
AuthorsGuenther, E.L. / Sawaya, M.R. / Ivanova, M. / Eisenberg, D.S.
CitationJournal: Nature / Year: 2015
Title: Structure of the toxic core of α-synuclein from invisible crystals.
Authors: Jose A Rodriguez / Magdalena I Ivanova / Michael R Sawaya / Duilio Cascio / Francis E Reyes / Dan Shi / Smriti Sangwan / Elizabeth L Guenther / Lisa M Johnson / Meng Zhang / Lin Jiang / Mark ...Authors: Jose A Rodriguez / Magdalena I Ivanova / Michael R Sawaya / Duilio Cascio / Francis E Reyes / Dan Shi / Smriti Sangwan / Elizabeth L Guenther / Lisa M Johnson / Meng Zhang / Lin Jiang / Mark A Arbing / Brent L Nannenga / Johan Hattne / Julian Whitelegge / Aaron S Brewster / Marc Messerschmidt / Sébastien Boutet / Nicholas K Sauter / Tamir Gonen / David S Eisenberg /
Abstract: The protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term ...The protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 Å resolution structure demonstrates that this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face β-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils.
History
DepositionOct 6, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 26, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 9, 2015Group: Database references
Revision 1.2Sep 23, 2015Group: Database references
Revision 1.3Oct 7, 2015Group: Database references
Revision 1.4Feb 28, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.5Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-synuclein


Theoretical massNumber of molelcules
Total (without water)8161
Polymers8161
Non-polymers00
Water543
1
A: Alpha-synuclein
x 10


Theoretical massNumber of molelcules
Total (without water)8,16010
Polymers8,16010
Non-polymers00
Water18010
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_535x,y-2,z1
crystal symmetry operation1_545x,y-1,z1
crystal symmetry operation1_565x,y+1,z1
crystal symmetry operation1_575x,y+2,z1
crystal symmetry operation4_535-x+1/2,y-3/2,-z1
crystal symmetry operation4_545-x+1/2,y-1/2,-z1
crystal symmetry operation4_555-x+1/2,y+1/2,-z1
crystal symmetry operation4_565-x+1/2,y+3/2,-z1
crystal symmetry operation4_575-x+1/2,y+5/2,-z1
Unit cell
Length a, b, c (Å)61.864, 4.799, 17.263
Angle α, β, γ (deg.)90.00, 104.13, 90.00
Int Tables number5
Space group name H-MC121
DetailsThe biological unit is a pair of beta-sheets. One sheet is composed of chain A and unit cell translations along the b dimension (for example, x,y+1,z, etc.). The other sheet is composed of the symmetry mate -x+1/2,y+1/2,-z+1, and its unit cell translations along b (for example, -x+1/2,y+3/2,-z+1, etc.).

-
Components

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


Mass: 815.953 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: Synthetic peptide AVVTGVTAV corresponding to segment 69-77 of human alpha-synuclein
Source: (synth.) Homo sapiens (human) / References: UniProt: P37840
#2: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 1.52 Å3/Da / Density % sol: 19.22 %
Crystal growTemperature: 273 K / Method: vapor diffusion, hanging drop / pH: 4.6
Details: 0.9M Ammonium Phosphate, 0.1M Sodium Acetate, pH 4.6, vapor diffusion, hanging drop, temperature 273K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9791 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 23, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9791 Å / Relative weight: 1
ReflectionResolution: 1.85→100 Å / Num. all: 521 / Num. obs: 521 / % possible obs: 97.7 % / Observed criterion σ(I): -3 / Redundancy: 4.1 % / Rmerge(I) obs: 0.117 / Χ2: 0.961 / Net I/σ(I): 11.1
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.85-1.9240.248431.02197.7
1.92-1.994.20.29531.073196.4
1.99-2.0840.261461.351100
2.08-2.194.60.209570.884198.3
2.19-2.334.20.179521.2931100
2.33-2.514.40.202530.933189.8
2.51-2.764.10.125400.7641100
2.76-3.1640.099540.8051100
3.16-3.994.40.083570.818196.6
3.99-1003.50.075660.7331100

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
PHASER2.5.6phasing
REFMAC5refinement
PDB_EXTRACT3.15data extraction
DENZOdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: poly alanine

Resolution: 1.854→30 Å / Cor.coef. Fo:Fc: 0.978 / Cor.coef. Fo:Fc free: 0.961 / WRfactor Rfree: 0.236 / WRfactor Rwork: 0.19 / FOM work R set: 0.73 / SU B: 4.061 / SU ML: 0.112 / SU R Cruickshank DPI: 0.1735 / SU Rfree: 0.1526 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.173 / ESU R Free: 0.153 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2211 51 9.8 %RANDOM
Rwork0.1758 ---
all0.1802 470 --
obs0.1802 470 97.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 53.1 Å2 / Biso mean: 17.341 Å2 / Biso min: 6.25 Å2
Baniso -1Baniso -2Baniso -3
1--0.23 Å2-0 Å2-0.06 Å2
2---0.02 Å2-0 Å2
3---0.25 Å2
Refinement stepCycle: LAST / Resolution: 1.854→30 Å /
ProteinNucleic acidLigandSolventTotal
Num. atoms57 0 0 3 60
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0256
X-RAY DIFFRACTIONr_bond_other_d0.0110.0263
X-RAY DIFFRACTIONr_angle_refined_deg1.1231.96578
X-RAY DIFFRACTIONr_angle_other_deg0.6023141
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.19858
X-RAY DIFFRACTIONr_dihedral_angle_3_deg5.082156
X-RAY DIFFRACTIONr_chiral_restr0.0490.214
X-RAY DIFFRACTIONr_gen_planes_refined0.0020.0260
X-RAY DIFFRACTIONr_gen_planes_other00.028
X-RAY DIFFRACTIONr_mcbond_it5.8521.47535
X-RAY DIFFRACTIONr_mcbond_other5.8511.36434
X-RAY DIFFRACTIONr_mcangle_it8.4062.04642
LS refinement shellResolution: 1.854→2.072 Å / Total num. of bins used: 5
RfactorNum. reflection% reflection
Rfree0.286 12 -
Rwork0.248 125 -
all-137 -
obs--98.56 %

+
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