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- PDB-8g58: Tau (297-391) in vitro untwisted fibril -

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Basic information

Entry
Database: PDB / ID: 8g58
TitleTau (297-391) in vitro untwisted fibril
ComponentsMicrotubule-associated protein tauTau protein
KeywordsPROTEIN FIBRIL / AD tau core / untwisted filament
Function / homology
Function and homology information


plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / supramolecular fiber organization / Activation of AMPK downstream of NMDARs / regulation of microtubule cytoskeleton organization / cytoplasmic microtubule organization / stress granule assembly / regulation of cellular response to heat / axon cytoplasm / regulation of calcium-mediated signaling / positive regulation of microtubule polymerization / cellular response to brain-derived neurotrophic factor stimulus / somatodendritic compartment / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / synapse organization / response to lead ion / microglial cell activation / regulation of synaptic plasticity / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / cytoplasmic ribonucleoprotein granule / memory / microtubule cytoskeleton organization / cellular response to reactive oxygen species / SH3 domain binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / protein-macromolecule adaptor activity / single-stranded DNA binding / cell-cell signaling / cellular response to heat / cell body / actin binding / growth cone / protein-folding chaperone binding / double-stranded DNA binding / microtubule binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / neuron projection / nuclear speck / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding
Similarity search - Function
: / Microtubule associated protein, tubulin-binding repeat / Microtubule-associated protein Tau / Tau and MAP protein, tubulin-binding repeat / Tau and MAP proteins tubulin-binding repeat signature. / Tau and MAP proteins tubulin-binding repeat profile.
Similarity search - Domain/homology
Microtubule-associated protein tau
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLID-STATE NMR / simulated annealing
AuthorsDuan, P. / Dregni, A.J. / Mammeri, N.E. / Hong, M.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Aging (NIH/NIA)AG059661 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM132079 United States
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2023
Title: Structure of the nonhelical filament of the Alzheimer's disease tau core.
Authors: Duan, P. / Dregni, A.J. / Mammeri, N.E. / Hong, M.
History
DepositionFeb 12, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 8, 2023Provider: repository / Type: Initial release
Revision 1.1May 15, 2024Group: Database references / Category: database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Microtubule-associated protein tau
B: Microtubule-associated protein tau
C: Microtubule-associated protein tau
D: Microtubule-associated protein tau
E: Microtubule-associated protein tau
F: Microtubule-associated protein tau
G: Microtubule-associated protein tau
H: Microtubule-associated protein tau
I: Microtubule-associated protein tau
J: Microtubule-associated protein tau


Theoretical massNumber of molelcules
Total (without water)103,18810
Polymers103,18810
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: NMR Distance Restraints
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area52190 Å2
ΔGint-200 kcal/mol
Surface area22350 Å2
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 5296structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein
Microtubule-associated protein tau / Tau protein / Neurofibrillary tangle protein / Paired helical filament-tau / PHF-tau


Mass: 10318.810 Da / Num. of mol.: 10
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPT, MAPTL, MTBT1, TAU / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P10636

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Experimental details

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Experiment

ExperimentMethod: SOLID-STATE NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
112isotropic21D 13C CP
122isotropic21D 15N CP
132isotropic230ms 2D CC
142isotropic22D NCACB
152isotropic1400 ms 2D CC
162isotropic23D NCACX
172isotropic23D NCOCX
182isotropic23D CONCACB
193isotropic11D 13C CP
1103isotropic11D 15N CP
1113isotropic126ms 2D CC
1123isotropic12D NCA
1133isotropic12D HC INEPT
1143isotropic1400ms 2D CC
1154isotropic150ms 2D CC
1164isotropic12D NCA
1174isotropic1400ms 2D CC

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Sample preparation

Details
TypeSolution-IDContentsLabelSolvent system
fibrous protein21 uM UCN Tau (297-391), 100% H2OUCN100% H2O
fibrous protein30.5 uM UCN Tau (297-391), 0.5 uM Tau (297-391), 100% H2O50% diluted100% H2O
fibrous protein41 uM 1,3-Glycerol,15N Tau (297-391), 100% H2O1,3-Gly100% H2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
1 uMTau (297-391)UCN2
0.5 uMTau (297-391)UCN3
0.5 uMunlabeled Tau (297-391)natural abundance3
1 uMTau (297-391)1,3-Glycerol,15N4
Sample conditionsDetails: 200mM MgCl2, 10 mM potassium phosphate buffer, 10 mM DTT
Ionic strength: 0.6 M / Label: 200mM MgCl2 / pH: 5.0 / Pressure: 1 atm / Temperature: 287 K / Temperature err: 2

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker 800Bruker800 8001
Bruker 900Bruker900 9002

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Processing

NMR software
NameDeveloperClassification
TopSpinBruker Biospincollection
TopSpinBruker Biospinprocessing
CcpNmr AnalysisCCPNchemical shift assignment
CcpNmr AnalysisCCPNpeak picking
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorerefinement
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorestructure calculation
RefinementMethod: simulated annealing / Software ordinal: 6
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 5296 / Conformers submitted total number: 10

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