+
Open data
-
Basic information
Entry | Database: PDB / ID: 7pqc | ||||||
---|---|---|---|---|---|---|---|
Title | tau-microtubule structural ensemble based on CryoEM data | ||||||
![]() |
| ||||||
![]() | STRUCTURAL PROTEIN / Complex | ||||||
Function / homology | ![]() Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling ...Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Aggrephagy / Resolution of Sister Chromatid Cohesion / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Separation of Sister Chromatids / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / COPI-mediated anterograde transport / plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / 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 / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / intracellular distribution of mitochondria / 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 / apolipoprotein binding / negative regulation of mitochondrial membrane potential / protein polymerization / axolemma / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / cytoplasmic microtubule organization / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / 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 / response to lead ion / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / synapse organization / microglial cell activation / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / structural constituent of cytoskeleton / memory / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton / neuron projection development / cell-cell signaling / mitotic cell cycle / protein-macromolecule adaptor activity Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / negative staining / cryo EM / Resolution: 4.1 Å | ||||||
![]() | Brotzakis, Z.F. / Vendruscolo, M. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms. Authors: Z Faidon Brotzakis / Philip R Lindstedt / Ross J Taylor / Dillon J Rinauro / Nicholas C T Gallagher / Gonçalo J L Bernardes / Michele Vendruscolo / ![]() ![]() Abstract: Tau is a microtubule-associated protein that regulates the stability of microtubules. We use metainference cryoelectron microscopy, an integrative structural biology approach, to determine an ...Tau is a microtubule-associated protein that regulates the stability of microtubules. We use metainference cryoelectron microscopy, an integrative structural biology approach, to determine an ensemble of conformations representing the structure and dynamics of a tau-microtubule complex comprising the entire microtubule-binding region of tau (residues 202-395). We thus identify the ground state of the complex and a series of excited states of lower populations. A comparison of the interactions in these different states reveals positions along the tau sequence that are important to determine the overall stability of the tau-microtubule complex. This analysis leads to the identification of positions where phosphorylation and acetylation events have destabilizing effects, which we validate by using site-specific post-translationally modified tau variants obtained by chemical mutagenesis. Taken together, these results illustrate how the simultaneous determination of ground and excited states of macromolecular complexes reveals functional and regulatory mechanisms. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 992.2 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 772.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 7522M ![]() 7pqpC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Protein , 3 types, 15 molecules ACEGIKMBDFHJLNO
#1: Protein | Mass: 49907.770 Da / Num. of mol.: 7 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Protein | Mass: 50204.445 Da / Num. of mol.: 7 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Protein | | Mass: 20740.863 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|
-Non-polymers , 3 types, 21 molecules ![](data/chem/img/GDP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
#4: Chemical | ChemComp-GDP / #5: Chemical | ChemComp-GTP / #6: Chemical | ChemComp-MG / |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component |
| ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||
Buffer solution | pH: 6.8 | ||||||||||||||||||||||||||||
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: YES / Vitrification applied: YES | ||||||||||||||||||||||||||||
EM staining | Type: NONE / Material: SDS PAGE and Coomassie | ||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-
Electron microscopy imaging
Microscopy | Model: FEI TITAN |
---|---|
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: GATAN LIQUID NITROGEN |
Image recording | Electron dose: 27.5 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
CTF correction | Details: Images were drift-corrected using UCSF motioncorr software . CTFFIND4 was used to estimate CTFs for the drift-corrected images Type: PHASE FLIPPING ONLY |
---|---|
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25963 / Symmetry type: POINT |