+Open data
-Basic information
Entry | Database: PDB / ID: 6nk4 | ||||||
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Title | KVQIINKKL, crystal structure of a tau protein fragment | ||||||
Components | Microtubule-associated protein tauTau protein | ||||||
Keywords | STRUCTURAL PROTEIN / Amyloid / tau / Alzheimer's Disease / tauopathy / MAPT | ||||||
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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON CRYSTALLOGRAPHY / electron crystallography / MOLECULAR REPLACEMENT / cryo EM / Resolution: 1.994 Å | ||||||
Model details | Crystal structure KVQIINKL from the microtubule binding region of tau protein reveals a tightly ...Crystal structure KVQIINKL from the microtubule binding region of tau protein reveals a tightly packed steric zipper | ||||||
Authors | Eisenberg, D.S. / Boyer, D.R. / Sawaya, M.R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2021 Title: Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosines. Authors: Catharine Shipps / H Ray Kelly / Peter J Dahl / Sophia M Yi / Dennis Vu / David Boyer / Calina Glynn / Michael R Sawaya / David Eisenberg / Victor S Batista / Nikhil S Malvankar / Abstract: Proteins are commonly known to transfer electrons over distances limited to a few nanometers. However, many biological processes require electron transport over far longer distances. For example, ...Proteins are commonly known to transfer electrons over distances limited to a few nanometers. However, many biological processes require electron transport over far longer distances. For example, soil and sediment bacteria transport electrons, over hundreds of micrometers to even centimeters, via putative filamentous proteins rich in aromatic residues. However, measurements of true protein conductivity have been hampered by artifacts due to large contact resistances between proteins and electrodes. Using individual amyloid protein crystals with atomic-resolution structures as a model system, we perform contact-free measurements of intrinsic electronic conductivity using a four-electrode approach. We find hole transport through micrometer-long stacked tyrosines at physiologically relevant potentials. Notably, the transport rate through tyrosines (10 s) is comparable to cytochromes. Our studies therefore show that amyloid proteins can efficiently transport charges, under ordinary thermal conditions, without any need for redox-active metal cofactors, large driving force, or photosensitizers to generate a high oxidation state for charge injection. By measuring conductivity as a function of molecular length, voltage, and temperature, while eliminating the dominant contribution of contact resistances, we show that a multistep hopping mechanism (composed of multiple tunneling steps), not single-step tunneling, explains the measured conductivity. Combined experimental and computational studies reveal that proton-coupled electron transfer confers conductivity; both the energetics of the proton acceptor, a neighboring glutamine, and its proximity to tyrosine influence the hole transport rate through a proton rocking mechanism. Surprisingly, conductivity increases 200-fold upon cooling due to higher availability of the proton acceptor by increased hydrogen bonding. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6nk4.cif.gz | 13.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nk4.ent.gz | 5.2 KB | Display | PDB format |
PDBx/mmJSON format | 6nk4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nk/6nk4 ftp://data.pdbj.org/pub/pdb/validation_reports/nk/6nk4 | HTTPS FTP |
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-Related structure data
Related structure data | 5v5bS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
#1: Protein/peptide | Mass: 1086.390 Da / Num. of mol.: 1 / Fragment: repeat 2 peptide (UNP residues 591-599) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P10636 |
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#2: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON CRYSTALLOGRAPHY / Number of used crystals: 1 |
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EM experiment | Aggregation state: 3D ARRAY / 3D reconstruction method: electron crystallography |
-Sample preparation
Component | Name: KVQIINKKL Tau peptide / Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
EM crystal formation | Instrument: hanging drop vapor diffusion / Atmosphere: air / Details: 0.2 M lithium citrate, 20% PEG3350 / Lipid mixture: none / Temperature: 291 K |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
Crystal | Density Matthews: 2.54 Å3/Da / Density % sol: 51.58 % |
Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / Details: 0.2 M lithium citrate, 20% PEG3350 |
-Data collection
Microscopy | Model: FEI TECNAI 20 | ||||||||||||||||||||||||||||||||||||||||||
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM | ||||||||||||||||||||||||||||||||||||||||||
Electron lens | Mode: DIFFRACTION | ||||||||||||||||||||||||||||||||||||||||||
Image recording | Electron dose: 0.1 e/Å2 / Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) | ||||||||||||||||||||||||||||||||||||||||||
EM diffraction | Camera length: 1850 mm | ||||||||||||||||||||||||||||||||||||||||||
EM diffraction shell | Resolution: 2→2.15 Å / Fourier space coverage: 95.7 % / Multiplicity: 4.9 / Num. of structure factors: 174 / Phase residual: 0.1 ° | ||||||||||||||||||||||||||||||||||||||||||
EM diffraction stats | Fourier space coverage: 97.1 % / High resolution: 2 Å / Num. of intensities measured: 943 / Num. of structure factors: 943 / Phase error: 0 ° / Phase residual: 0.1 ° / Phase error rejection criteria: 0 / Rmerge: 0.244 / Rsym: 0.244 | ||||||||||||||||||||||||||||||||||||||||||
Diffraction | Mean temperature: 88 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||
Diffraction source | Source: ELECTRON MICROSCOPE / Type: TECNAI F20 TEM / Wavelength: 0.0251 Å | ||||||||||||||||||||||||||||||||||||||||||
Detector | Type: TVIPS F416 CMOS CAMERA / Detector: CMOS / Date: Jan 19, 2017 | ||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: electron | ||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.0251 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.994→90 Å / Num. obs: 943 / % possible obs: 97.1 % / Redundancy: 6 % / Biso Wilson estimate: 22.14 Å2 / Rmerge(I) obs: 0.244 / Χ2: 1.394 / Net I/σ(I): 2.7 | ||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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EM software | Name: PHENIX / Version: 1.11.1_2575 / Category: model refinement | ||||||||||||||||||||||||
EM 3D crystal entity | ∠α: 90 ° / ∠β: 90 ° / ∠γ: 90 ° / A: 62.906 Å / B: 62.906 Å / C: 4.832 Å / Space group name: P61 / Space group num: 169 | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution method: DIFFRACTION PATTERN/LAYERLINES / Symmetry type: 3D CRYSTAL | ||||||||||||||||||||||||
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 5V5B Resolution: 1.994→27.24 Å / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 19.1
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||
Displacement parameters | Biso max: 51.32 Å2 / Biso mean: 18.6573 Å2 / Biso min: 3.33 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.994→54.478 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.9944→27.24 Å / Rfactor Rfree error: 0
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