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Yorodumi- PDB-1s78: Insights into ErbB signaling from the structure of the ErbB2-pert... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1s78 | |||||||||
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Title | Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex | |||||||||
Components |
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Keywords | TRANSFERASE / receptor-antibody complex / Fab fragment / cysteine-rich domain / leucine-rich repeat | |||||||||
Function / homology | Function and homology information negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / PLCG1 events in ERBB2 signaling / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / ERBB2-EGFR signaling pathway / ERBB2 Activates PTK6 Signaling / semaphorin receptor complex ...negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / PLCG1 events in ERBB2 signaling / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / ERBB2-EGFR signaling pathway / ERBB2 Activates PTK6 Signaling / semaphorin receptor complex / regulation of microtubule-based process / ErbB-3 class receptor binding / ERBB2 Regulates Cell Motility / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / PI3K events in ERBB2 signaling / neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of Rho protein signal transduction / neuromuscular junction development / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / ERBB2-ERBB3 signaling pathway / positive regulation of transcription by RNA polymerase I / oligodendrocyte differentiation / semaphorin-plexin signaling pathway / cellular response to epidermal growth factor stimulus / Signaling by ERBB2 / positive regulation of cell adhesion / positive regulation of protein targeting to membrane / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / regulation of angiogenesis / neurogenesis / SHC1 events in ERBB2 signaling / coreceptor activity / regulation of ERK1 and ERK2 cascade / Schwann cell development / basal plasma membrane / positive regulation of epithelial cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / myelination / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Downregulation of ERBB2:ERBB3 signaling / Constitutive Signaling by Overexpressed ERBB2 / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / positive regulation of translation / receptor protein-tyrosine kinase / Downregulation of ERBB2 signaling / ruffle membrane / wound healing / neuromuscular junction / peptidyl-tyrosine phosphorylation / neuron differentiation / transmembrane signaling receptor activity / receptor tyrosine kinase binding / cellular response to growth factor stimulus / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / myelin sheath / presynaptic membrane / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / heart development / RAF/MAP kinase cascade / positive regulation of cell growth / basolateral plasma membrane / protein tyrosine kinase activity / receptor complex / positive regulation of MAPK cascade / cell surface receptor signaling pathway / endosome membrane / early endosome / intracellular signal transduction / positive regulation of protein phosphorylation / apical plasma membrane / immune response / protein heterodimerization activity / protein phosphorylation / signaling receptor binding / positive regulation of cell population proliferation / negative regulation of apoptotic process / perinuclear region of cytoplasm / signal transduction / extracellular space / nucleoplasm / ATP binding / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.25 Å | |||||||||
Authors | Franklin, M.C. / Carey, K.D. / Vajdos, F.F. / Leahy, D.J. / de Vos, A.M. / Sliwkowski, M.X. | |||||||||
Citation | Journal: Cancer Cell / Year: 2004 Title: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Authors: Franklin, M.C. / Carey, K.D. / Vajdos, F.F. / Leahy, D.J. / De Vos, A.M. / Sliwkowski, M.X. #1: Journal: Nature / Year: 2003 Title: Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab Authors: Cho, H.S. / Mason, K. / Ramyar, K.X. / Stanley, A.M. / Gabelli, S.B. / Denney Jr., D.W. / Leahy, D.J. #2: Journal: J.Mol.Biol. / Year: 2002 Title: Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis Authors: Vajdos, F.F. / Adams, C.W. / Breece, T.N. / Presta, L.G. / de Vos, A.M. / Sidhu, S.S. #3: Journal: Cancer Cell / Year: 2002 Title: Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth Authors: Agus, D.B. / Akita, R.W. / Fox, W.D. / Lewis, G.D. / Higgins, B. / Pisacane, P.I. / Lofgren, J.A. / Tindell, C. / Evans, D.P. / Maiese, K. / Scher, H.I. / Sliwkowski, M.X. | |||||||||
History |
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Remark 999 | SEQUENCE The sequences of the chains C,E and D,F were not deposited into any sequence database. ...SEQUENCE The sequences of the chains C,E and D,F were not deposited into any sequence database. Residues C110-C214 and D113-D216 lie in a region of very poor electron density and have not been well refined. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1s78.cif.gz | 388.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1s78.ent.gz | 314.8 KB | Display | PDB format |
PDBx/mmJSON format | 1s78.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1s78_validation.pdf.gz | 2.8 MB | Display | wwPDB validaton report |
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Full document | 1s78_full_validation.pdf.gz | 2.9 MB | Display | |
Data in XML | 1s78_validation.xml.gz | 68.6 KB | Display | |
Data in CIF | 1s78_validation.cif.gz | 93.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/s7/1s78 ftp://data.pdbj.org/pub/pdb/validation_reports/s7/1s78 | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 68794.086 Da / Num. of mol.: 2 / Fragment: extracellular domain (residues 23-646) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERBB2, HER2, NGL, NEU / Organ (production host): ovary / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P04626, EC: 2.7.1.112 |
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-Antibody , 2 types, 4 molecules CEDF
#2: Antibody | Mass: 23548.152 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Plasmid: 2C4574 / Production host: Escherichia coli (E. coli) / Strain (production host): 16C9 / References: UniProt: Q7Z3Y4*PLUS #3: Antibody | Mass: 24158.006 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Plasmid: 2C4574 / Production host: Escherichia coli (E. coli) / Strain (production host): 16C9 |
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-Sugars , 3 types, 7 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #6: Sugar | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 4 Å3/Da / Density % sol: 69.01 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: PEG 3350, ammonium formate, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Nov 19, 2001 |
Radiation | Monochromator: single crystal Si(220) monochromator, cylindrically bent Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.25→30 Å / Num. all: 56393 / Num. obs: 56351 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 8.2 % / Biso Wilson estimate: 97.8 Å2 / Rmerge(I) obs: 0.116 / Rsym value: 0.116 / Net I/σ(I): 19.3 |
Reflection shell | Resolution: 3.25→3.37 Å / Redundancy: 8.3 % / Rmerge(I) obs: 0.691 / Mean I/σ(I) obs: 3.3 / Num. unique all: 5496 / Rsym value: 0.691 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: Rat ErbB2 extracellular domain (PDB code 1N8Y) and uncomplexed pertuzumab Fab (PDB code 1L7I) Resolution: 3.25→15 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.88 / SU B: 22.571 / SU ML: 0.381 / TLS residual ADP flag: LIKELY RESIDUAL / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.479 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 10.586 Å2
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Refinement step | Cycle: LAST / Resolution: 3.25→15 Å
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Refine LS restraints |
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Refine LS restraints NCS | Dom-ID: 1 / Auth asym-ID: A / Refine-ID: X-RAY DIFFRACTION
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LS refinement shell | Resolution: 3.25→3.33 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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