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- PDB-6dc8: Fab/epitope complex of mouse monoclonal antibody 8B2 targeting a ... -

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Basic information

Entry
Database: PDB / ID: 6dc8
TitleFab/epitope complex of mouse monoclonal antibody 8B2 targeting a non-phosphorylated tau epitope.
Components
  • IgG heavy chain
  • IgG light chain
  • Microtubule-associated protein tau
KeywordsIMMUNE SYSTEM / monoclonal antibody / fab / tau / phosphorylation state -specific antibody
Function / homology
Function and homology information


plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / regulation of long-term synaptic depression ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / regulation of long-term synaptic depression / tubulin complex / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / rRNA metabolic process / axonal transport of mitochondrion / regulation of mitochondrial fission / axon development / central nervous system neuron development / intracellular distribution of mitochondria / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / negative regulation of mitochondrial membrane potential / apolipoprotein binding / glial cell projection / axolemma / protein polymerization / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / neurofibrillary tangle assembly / Activation of AMPK downstream of NMDARs / synapse assembly / regulation of cellular response to heat / supramolecular fiber organization / positive regulation of protein localization / regulation of calcium-mediated signaling / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / cytoplasmic microtubule organization / axon cytoplasm / positive regulation of microtubule polymerization / stress granule assembly / phosphatidylinositol binding / regulation of microtubule cytoskeleton organization / nuclear periphery / protein phosphatase 2A binding / positive regulation of superoxide anion generation / cellular response to reactive oxygen species / astrocyte activation / Hsp90 protein binding / microglial cell activation / cellular response to nerve growth factor stimulus / response to lead ion / synapse organization / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / SH3 domain binding / memory / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / neuron projection development / cell-cell signaling / single-stranded DNA binding / protein-folding chaperone binding / actin binding / cellular response to heat / microtubule cytoskeleton / cell body / growth cone / double-stranded DNA binding / microtubule binding / protein-macromolecule adaptor activity / dendritic spine / sequence-specific DNA binding / microtubule / amyloid fibril formation / learning or memory / neuron projection / regulation of autophagy / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding / RNA binding / extracellular region / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Microtubule-associated protein Tau / Microtubule associated protein, tubulin-binding repeat / Tau and MAP protein, tubulin-binding repeat / Tau and MAP proteins tubulin-binding repeat signature. / Tau and MAP proteins tubulin-binding repeat profile. / : / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
PHOSPHATE ION / Microtubule-associated protein tau
Similarity search - Component
Biological speciesMus musculus (house mouse)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.799 Å
AuthorsChukwu, J.E. / Kong, X.-P.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS077239 United States
National Institutes of Health/National Institute on Aging (NIH/NIA)AG032611 United States
CitationJournal: MAbs / Year: 2019
Title: Structural characterization of monoclonal antibodies targeting C-terminal Ser404region of phosphorylated tau protein.
Authors: Chukwu, J.E. / Congdon, E.E. / Sigurdsson, E.M. / Kong, X.P.
History
DepositionMay 4, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 20, 2019Provider: repository / Type: Initial release
Revision 1.1Apr 3, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Nov 6, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
L: IgG light chain
H: IgG heavy chain
P: Microtubule-associated protein tau
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,3097
Polymers50,9383
Non-polymers3714
Water10,251569
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5500 Å2
ΔGint-35 kcal/mol
Surface area19340 Å2
MethodPISA
Unit cell
Length a, b, c (Å)68.836, 68.836, 198.853
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212
Components on special symmetry positions
IDModelComponents
11H-635-

HOH

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Components

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Protein/peptide , 1 types, 1 molecules P

#3: Protein/peptide Microtubule-associated protein tau / Neurofibrillary tangle protein / Paired helical filament-tau / PHF-tau


Mass: 3268.639 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P10636

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Antibody , 2 types, 2 molecules LH

#1: Antibody IgG light chain


Mass: 24237.729 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
#2: Antibody IgG heavy chain


Mass: 23431.236 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)

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Non-polymers , 3 types, 573 molecules

#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 569 / Source method: isolated from a natural source / Formula: H2O

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Details

Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.31 Å3/Da / Density % sol: 46.8 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 23% polyethylene glycol 8000, 0.17 M ammonium acetate, and 0.085 M sodium cacodylate trihydrate pH 6.5

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL14-1 / Wavelength: 0.979 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Oct 9, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.79→40.3 Å / Num. obs: 45390 / % possible obs: 99.9 % / Redundancy: 1.1 % / Net I/σ(I): 14.5
Reflection shellResolution: 1.79→1.86 Å

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Processing

Software
NameVersionClassification
PHENIX(1.12_2829: ???)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
Cootmodel building
RefinementResolution: 1.799→40.302 Å / SU ML: 0.18 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 22.32 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2187 2252 4.96 %
Rwork0.1791 --
obs0.1811 45380 99.91 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.799→40.302 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3397 0 23 569 3989
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0063506
X-RAY DIFFRACTIONf_angle_d0.9124778
X-RAY DIFFRACTIONf_dihedral_angle_d13.8832076
X-RAY DIFFRACTIONf_chiral_restr0.059535
X-RAY DIFFRACTIONf_plane_restr0.005603
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.7992-1.83840.311120.2342649X-RAY DIFFRACTION100
1.8384-1.88110.28341210.21542664X-RAY DIFFRACTION100
1.8811-1.92820.21851370.20582641X-RAY DIFFRACTION100
1.9282-1.98030.22371280.1982658X-RAY DIFFRACTION100
1.9803-2.03860.25341440.18812652X-RAY DIFFRACTION100
2.0386-2.10440.23811350.19072661X-RAY DIFFRACTION100
2.1044-2.17960.26561330.18552642X-RAY DIFFRACTION100
2.1796-2.26680.24571740.18742654X-RAY DIFFRACTION100
2.2668-2.370.23661520.1922673X-RAY DIFFRACTION100
2.37-2.49490.23761330.19492657X-RAY DIFFRACTION100
2.4949-2.65120.22921460.20372700X-RAY DIFFRACTION100
2.6512-2.85590.24351370.19492694X-RAY DIFFRACTION100
2.8559-3.14320.2281470.18732723X-RAY DIFFRACTION100
3.1432-3.59770.18561310.16982738X-RAY DIFFRACTION100
3.5977-4.53180.19141700.14492765X-RAY DIFFRACTION100
4.5318-40.3120.19371520.16382957X-RAY DIFFRACTION100

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