[English] 日本語
Yorodumi
- PDB-4hrn: Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4hrn
TitleStructural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2
Components
  • Designed Ankyrin Repeat Protein H10-2-G
  • Receptor tyrosine-protein kinase erbB-2
KeywordsTRANSFERASE/DE NOVO PROTEIN / TRANSFERASE-DE NOVO PROTEIN complex
Function / homology
Function and homology information


negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / semaphorin receptor complex / regulation of microtubule-based process / ErbB-3 class receptor binding / Sema4D induced cell migration and growth-cone collapse ...negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / semaphorin receptor complex / regulation of microtubule-based process / ErbB-3 class receptor binding / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / PLCG1 events in ERBB2 signaling / ERBB2-EGFR signaling pathway / positive regulation of Rho protein signal transduction / ERBB2 Activates PTK6 Signaling / 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 / ERBB2 Regulates Cell Motility / semaphorin-plexin signaling pathway / PI3K events in ERBB2 signaling / positive regulation of protein targeting to membrane / positive regulation of cell adhesion / regulation of angiogenesis / coreceptor activity / Schwann cell development / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / myelination / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / Downregulation of ERBB2:ERBB3 signaling / transmembrane receptor protein tyrosine kinase activity / neurogenesis / SHC1 events in ERBB2 signaling / Constitutive Signaling by Overexpressed ERBB2 / regulation of ERK1 and ERK2 cascade / basal plasma membrane / positive regulation of translation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of epithelial cell proliferation / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / neuromuscular junction / wound healing / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / receptor protein-tyrosine kinase / neuron differentiation / receptor tyrosine kinase binding / cellular response to growth factor stimulus / Downregulation of ERBB2 signaling / ruffle membrane / peptidyl-tyrosine phosphorylation / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / transmembrane signaling receptor activity / PIP3 activates AKT signaling / myelin sheath / presynaptic membrane / heart development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / positive regulation of cell growth / basolateral plasma membrane / protein tyrosine kinase activity / positive regulation of MAPK cascade / cell surface receptor signaling pathway / receptor complex / early endosome / endosome membrane / intracellular signal transduction / positive regulation of protein phosphorylation / apical plasma membrane / 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 / nucleoplasm / ATP binding / membrane / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A domain 2 / Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A, domain 2 / Ankyrin repeat-containing domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain ...Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A domain 2 / Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A, domain 2 / Ankyrin repeat-containing domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat / Ribbon / Alpha Horseshoe / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Receptor tyrosine-protein kinase erbB-2
Similarity search - Component
Biological speciessynthetic (others)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.65 Å
AuthorsJost, C. / Schilling, J. / Plueckthun, A.
CitationJournal: Structure / Year: 2013
Title: Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2.
Authors: Jost, C. / Schilling, J. / Tamaskovic, R. / Schwill, M. / Honegger, A. / Plueckthun, A.
History
DepositionOct 28, 2012Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Oct 16, 2013Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2013Group: Structure summary
Revision 1.2Nov 8, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Designed Ankyrin Repeat Protein H10-2-G
B: Designed Ankyrin Repeat Protein H10-2-G
C: Receptor tyrosine-protein kinase erbB-2
D: Receptor tyrosine-protein kinase erbB-2


Theoretical massNumber of molelcules
Total (without water)52,5534
Polymers52,5534
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4740 Å2
ΔGint-31 kcal/mol
Surface area16150 Å2
MethodPISA
2
A: Designed Ankyrin Repeat Protein H10-2-G
D: Receptor tyrosine-protein kinase erbB-2


Theoretical massNumber of molelcules
Total (without water)26,2772
Polymers26,2772
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1520 Å2
ΔGint-10 kcal/mol
Surface area8820 Å2
MethodPISA
3
B: Designed Ankyrin Repeat Protein H10-2-G
C: Receptor tyrosine-protein kinase erbB-2


Theoretical massNumber of molelcules
Total (without water)26,2772
Polymers26,2772
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1410 Å2
ΔGint-11 kcal/mol
Surface area9140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)195.000, 195.000, 112.000
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number155
Space group name H-MH32

-
Components

#1: Protein Designed Ankyrin Repeat Protein H10-2-G


Mass: 14618.437 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic (others) / Plasmid: pQE30 / Production host: Escherichia coli (E. coli) / Strain (production host): XL1-blue
#2: Protein Receptor tyrosine-protein kinase erbB-2 / Metastatic lymph node gene 19 protein / MLN 19 / Proto-oncogene Neu / Proto-oncogene c-ErbB-2 / ...Metastatic lymph node gene 19 protein / MLN 19 / Proto-oncogene Neu / Proto-oncogene c-ErbB-2 / Tyrosine kinase-type cell surface receptor HER2 / p185erbB2


Mass: 11658.186 Da / Num. of mol.: 2 / Fragment: Domain IV, UNP RESIDUES 529-625 / Mutation: N8D, N49D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ERBB2, HER2, MLN19, NEU, NGL / Plasmid: pFL / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P04626, receptor protein-tyrosine kinase

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.9 Å3/Da / Density % sol: 68.45 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 4
Details: 0.05M succinic acid, 29% ammonium sulfate, pH 4.0, vapor diffusion, temperature 293K

-
Data collection

DiffractionMean temperature: 90 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Aug 22, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionHighest resolution: 2.65 Å / Num. obs: 23767 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 64.811 Å2 / Rmerge(I) obs: 0.041 / Net I/σ(I): 26.42
Reflection shell

Diffraction-ID: 1

Resolution (Å)Highest resolution (Å)Rmerge F obsRmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsRrim(I) all% possible all
2.65-2.720.6270.5113.548239173617350.57599.9
2.72-2.790.4710.3824.638448171117110.428100
2.79-2.870.3780.3215.828674166516620.35899.8
2.87-2.960.2330.2227.988481160116010.247100
2.96-3.060.1880.16410.388174155115490.18399.9
3.06-3.170.1460.12912.877931150915080.14499.9
3.17-3.290.1010.09716.377596145814580.108100
3.29-3.420.0720.06820.837040139313930.076100
3.42-3.570.0550.05125.556492136313630.057100
3.57-3.750.0390.04131.186514130513030.04699.8
3.75-3.950.0280.03537.786474121212120.039100
3.95-4.190.0230.0342.956051115211510.03399.9
4.19-4.480.0210.02845.875647109710970.031100
4.48-4.840.0190.02746.095144102510250.03100
4.84-5.30.0190.02547.8643459409390.02899.9
5.3-5.930.0180.02550.2243598658640.02899.9
5.93-6.840.0160.02256.3238917507490.02499.9
6.84-8.380.0110.01869.4732426516490.0299.7
8.38-11.850.010.01772.2522845115090.01999.6
11.850.010.01677.3914292962890.01897.6

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2.65 Å48.75 Å
Translation2.65 Å48.75 Å

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHASER2.3.0phasing
REFMACrefinement
PDB_EXTRACT3.11data extraction
PHENIX1.8_1069refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1N8Z, 2JAB

1n8z

2jab


Resolution: 2.65→48.75 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.31 / σ(F): 1.99 / Phase error: 30.67 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2494 1218 5.13 %
Rwork0.2177 --
obs0.2194 23756 99.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 86.21 Å2 / Biso mean: 47.5965 Å2 / Biso min: 27.12 Å2
Refinement stepCycle: LAST / Resolution: 2.65→48.75 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2808 0 0 0 2808

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more