[English] 日本語
Yorodumi
- PDB-6cew: Segment AMMAAA from the low complexity domain of TDP-43, residues... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cew
TitleSegment AMMAAA from the low complexity domain of TDP-43, residues 321-326
ComponentsAMMAAA
KeywordsPROTEIN FIBRIL / Amyloid / Steric-zipper
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.2 Å
AuthorsGuenther, E.L. / Cao, Q. / Lu, J. / Sawaya, M.R. / Eisenberg, D.S.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Aging (NIH/NIA)AG029430 United States
CitationJournal: Nat Struct Mol Biol / Year: 2018
Title: Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.
Authors: Elizabeth L Guenther / Qin Cao / Hamilton Trinh / Jiahui Lu / Michael R Sawaya / Duilio Cascio / David R Boyer / Jose A Rodriguez / Michael P Hughes / David S Eisenberg /
Abstract: The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is ...The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation.
History
DepositionFeb 12, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 18, 2018Provider: repository / Type: Initial release
Revision 1.1Jun 6, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.pdbx_database_id_DOI ..._citation.journal_abbrev / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Jun 13, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Mar 13, 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: AMMAAA
B: AMMAAA


Theoretical massNumber of molelcules
Total (without water)1,1292
Polymers1,1292
Non-polymers00
Water724
1
A: AMMAAA
B: AMMAAA
x 6


Theoretical massNumber of molelcules
Total (without water)6,77712
Polymers6,77712
Non-polymers00
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_455x-1,y,z1
crystal symmetry operation1_655x+1,y,z1
crystal symmetry operation4_555x+1/2,-y+1/2,-z1
crystal symmetry operation4_455x-1/2,-y+1/2,-z1
crystal symmetry operation4_655x+3/2,-y+1/2,-z1
Unit cell
Length a, b, c (Å)9.520, 15.440, 44.100
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein/peptide AMMAAA


Mass: 564.718 Da / Num. of mol.: 2 / Fragment: residues 321-326 / Source method: obtained synthetically
Details: Synthetic peptide AMMAAA corresponding to segment 321-326 of TDP-43
Source: (synth.) Homo sapiens (human)
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 4 / 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: 1.43 Å3/Da
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.3
Details: 1.3 M ammonium phosphate, 0.1 M sodium acetate pH 6.3

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9791 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 1, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9791 Å / Relative weight: 1
ReflectionResolution: 1.2→22.05 Å / Num. obs: 2209 / % possible obs: 96 % / Redundancy: 3.507 % / Biso Wilson estimate: 12.836 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.181 / Rrim(I) all: 0.214 / Χ2: 0.781 / Net I/σ(I): 3.16
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rrim(I) all% possible all
1.2-1.233.4970.6831.431450.6920.899.3
1.23-1.273.60.6171.621550.8860.72299.4
1.27-1.33.390.5791.571540.8440.67792.8
1.3-1.343.6240.4841.921250.8890.55988
1.34-1.393.7920.4412.331440.8190.51792.9
1.39-1.443.8580.5362.111340.8090.62199.3
1.44-1.493.6180.3672.531360.940.4398.6
1.49-1.553.5150.3572.711340.940.41595
1.55-1.623.6420.3442.81200.8960.40190.2
1.62-1.73.5860.2493.521110.9810.29797.4
1.7-1.793.3130.263.671150.9830.30393.5
1.79-1.93.4740.2374.141140.9730.27795
1.9-2.033.7250.2274.221020.9380.26397.1
2.03-2.193.5730.1794.57960.9690.20599
2.19-2.43.2290.1855.02960.9620.22198
2.4-2.693.4320.174.92810.9530.20998.8
2.69-3.13.1590.1315.44820.9470.15898.8
3.1-3.83.2740.1245.62620.9740.14495.4
3.8-5.373.0630.1035.87630.9970.126100
5.37-22.052.60.0314.484010.038100

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation1.53 Å22.08 Å
Translation1.53 Å22.08 Å

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
XSCALEdata scaling
PHASER2.7.17phasing
REFMACrefinement
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: IDEAL BETA STRAND

Resolution: 1.2→22.05 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.955 / SU B: 2.286 / SU ML: 0.045 / SU R Cruickshank DPI: 0.0612 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.061 / ESU R Free: 0.054
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2184 108 4.9 %RANDOM
Rwork0.1979 ---
obs0.1989 2078 96.09 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 25.38 Å2 / Biso mean: 9.425 Å2 / Biso min: 6.16 Å2
Baniso -1Baniso -2Baniso -3
1--0.64 Å20 Å2-0 Å2
2--0.85 Å20 Å2
3----0.21 Å2
Refinement stepCycle: final / Resolution: 1.2→22.05 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms74 0 0 4 78
Biso mean---22.32 -
Num. residues----12
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0278
X-RAY DIFFRACTIONr_bond_other_d0.0020.0288
X-RAY DIFFRACTIONr_angle_refined_deg1.4312.028103
X-RAY DIFFRACTIONr_angle_other_deg0.6293200
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.912512
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.1271515
X-RAY DIFFRACTIONr_chiral_restr0.0580.213
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.0285
X-RAY DIFFRACTIONr_gen_planes_other0.0010.0211
X-RAY DIFFRACTIONr_rigid_bond_restr2.0793166
X-RAY DIFFRACTIONr_sphericity_free20.46453
X-RAY DIFFRACTIONr_sphericity_bonded3.6265168
LS refinement shellResolution: 1.201→1.232 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.261 12 -
Rwork0.261 133 -
all-145 -
obs--98.64 %

+
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://pdbjlvh1.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