[English] 日本語
Yorodumi
- PDB-2l4k: Water refined solution structure of the human Grb7-SH2 domain in ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2l4k
TitleWater refined solution structure of the human Grb7-SH2 domain in complex with the 10 amino acid peptide pY1139
Components
  • Growth factor receptor-bound protein 7
  • Receptor tyrosine-protein kinase erbB-2
KeywordsSIGNALING PROTEIN / Grb7 / SH2 domain / erbB2 receptor / water refinement
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 / regulation of microtubule-based process / ErbB-3 class receptor binding / semaphorin receptor complex / 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 / regulation of microtubule-based process / ErbB-3 class receptor binding / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / RND1 GTPase cycle / PLCG1 events in ERBB2 signaling / ERBB2-EGFR signaling pathway / neuromuscular junction development / positive regulation of Rho protein signal transduction / ERBB2 Activates PTK6 Signaling / 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 / positive regulation of transcription by RNA polymerase I / ERBB2-ERBB3 signaling pathway / oligodendrocyte differentiation / ERBB2 Regulates Cell Motility / semaphorin-plexin signaling pathway / PI3K events in ERBB2 signaling / positive regulation of cell adhesion / RET signaling / positive regulation of protein targeting to membrane / regulation of angiogenesis / coreceptor activity / Schwann cell development / stress granule assembly / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / Tie2 Signaling / myelination / Downregulation of ERBB2:ERBB3 signaling / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / phosphatidylinositol binding / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / neurogenesis / basal plasma membrane / regulation of ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell projection / positive regulation of translation / positive regulation of epithelial cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / wound healing / neuromuscular junction / Signaling by ERBB2 ECD mutants / neuron differentiation / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / cellular response to growth factor stimulus / Downregulation of ERBB2 signaling / ruffle membrane / cytoplasmic stress granule / peptidyl-tyrosine phosphorylation / 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 / early endosome / cell surface receptor signaling pathway / negative regulation of translation / receptor complex / endosome membrane / intracellular signal transduction / positive regulation of cell migration / apical plasma membrane / positive regulation of protein phosphorylation / protein heterodimerization activity
Similarity search - Function
Growth factor receptor-bound protein 7 / : / BPS (Between PH and SH2) domain / BPS (Between PH and SH2) / GRB/APBB1IP / APBB1IP, PH domain / Ras association (RalGDS/AF-6) domain / Ras-associating (RA) domain profile. / Ras association (RalGDS/AF-6) domain / Ras-associating (RA) domain ...Growth factor receptor-bound protein 7 / : / BPS (Between PH and SH2) domain / BPS (Between PH and SH2) / GRB/APBB1IP / APBB1IP, PH domain / Ras association (RalGDS/AF-6) domain / Ras-associating (RA) domain profile. / Ras association (RalGDS/AF-6) domain / Ras-associating (RA) 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 / SH2 domain / SHC Adaptor Protein / 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 / PH domain / Growth factor receptor cysteine-rich domain superfamily / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Ubiquitin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Receptor tyrosine-protein kinase erbB-2 / Growth factor receptor-bound protein 7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / molecular dynamics simulated annealing, simulated annealing
Model detailsbest PROCHECK statistics, model 3
AuthorsPias, S.C. / Ivancic, M. / Brescia, P.J. / Johnson, D.L. / Smith, D.E. / Daly, R.J. / Lyons, B.A.
Citation
Journal: Protein Pept.Lett. / Year: 2012
Title: Water-Refined Solution Structure of the Human Grb7-SH2 Domain in Complex with the erbB2 Receptor Peptide pY1139.
Authors: Pias, S.C. / Johnson, D.L. / Smith, D.E. / Lyons, B.A.
#1: Journal: J.Biomol.Nmr / Year: 2003
Title: Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2.
Authors: Ivancic, M. / Daly, R.J. / Lyons, B.A.
#2: Journal: J.Biomol.Nmr / Year: 2002
Title: Assignment of backbone 1H, 13C, and 15N resonances of human Grb7-SH2 domain in complex with a phosphorylated peptide ligand.
Authors: Brescia, P.J. / Ivancic, M. / Lyons, B.A.
#3: Journal: To Be Published
History
DepositionOct 7, 2010Deposition site: BMRB / Processing site: RCSB
Revision 1.0Nov 17, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jul 25, 2012Group: Database references
Revision 1.3Oct 3, 2012Group: Database references

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Growth factor receptor-bound protein 7
B: Receptor tyrosine-protein kinase erbB-2


Theoretical massNumber of molelcules
Total (without water)14,9572
Polymers14,9572
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 50structures with the lowest energy and the fewest restraint violations
RepresentativeModel #1best procheck statistics
DetailsTHE DIMERIC ANNOTATION IN REMARK 350 REFERS TO THE TWO CHAINS OF THE ASSEMBLY (PROTEIN DOMAIN AND LIGAND)

-
Components

#1: Protein Growth factor receptor-bound protein 7 / GRB7 adapter protein / Epidermal growth factor receptor GRB-7 / B47


Mass: 13690.711 Da / Num. of mol.: 1 / Fragment: unp residues 415-532
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRB7 / Plasmid: pGEX-2T / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q14451
#2: Protein/peptide Receptor tyrosine-protein kinase erbB-2 / p185erbB2 / Tyrosine kinase-type cell surface receptor HER2 / Metastatic lymph node gene 19 protein / MLN 19


Mass: 1266.205 Da / Num. of mol.: 1 / Fragment: unp residues 1135-1144 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
References: UniProt: P04626, receptor protein-tyrosine kinase

-
Experimental details

-
Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1113D HNCA
1213D HN(CO)CA
1313D HN(CA)CB
1413D CBCA(CO)NH
1512D 15N HSQC
161CN NOESY-HSQC
1713D 15N NOESY-HSQC
1813D 13C NOESY-HSQC
1913D TOCSY-HSQC
11012D HMQC-J
11113D CBCANH
11213D (H)CCH-TOCSY
113113C, 15N→12C, 14N NOESY
114112C, 14N→13C, 15N NOESY
115112C, 14N→12C, 14N NOESY
116112C, 14N→12C, 14N TOCSY

-
Sample preparation

DetailsContents: 0.6-0.8 mM [U-100% 13C; U-100% 15N] Grb7-SH2 domain-1, 0.6-0.8 mM [U-100% 13C; U-100% 15N] pY1139 peptide-2, 52.2 mM acetic acid-3, 100 mM sodium chloride-4, 5 mM DTT-5, 1 mM EDTA-6, 0.9 mM ...Contents: 0.6-0.8 mM [U-100% 13C; U-100% 15N] Grb7-SH2 domain-1, 0.6-0.8 mM [U-100% 13C; U-100% 15N] pY1139 peptide-2, 52.2 mM acetic acid-3, 100 mM sodium chloride-4, 5 mM DTT-5, 1 mM EDTA-6, 0.9 mM sodium azide-7, 90% H2O/10% D2O
Solvent system: 90% H2O/10% D2O
Sample
Conc. (mg/ml)UnitsComponentIsotopic labelingConc. range (mg/ml)Solution-ID
mMGrb7-SH2 domain-1[U-100% 13C; U-100% 15N]0.6-0.81
mMpY1139 peptide-2[U-100% 13C; U-100% 15N]0.6-0.81
52.2 mMacetic acid-31
100 mMsodium chloride-41
5 mMDTT-51
1 mMEDTA-61
0.9 mMsodium azide-71
Sample conditionspH: 6.6 / Pressure: ambient / Temperature: 298 K

-
NMR measurement

NMR spectrometerType: Varian INOVA / Manufacturer: Varian / Model: INOVA / Field strength: 500 MHz

-
Processing

NMR software
NameVersionDeveloperClassification
AMBER9Case, Darden, Cheatham, III, Simmerling, Wang, Duke, Luo, ... and Kollmrefinement
CNS1.1Brunger, Adams, Clore, Gros, Nilges and Readstructure calculation
RefinementMethod: molecular dynamics simulated annealing, simulated annealing
Software ordinal: 1
Details: Refinement with AMBER software, using implicit water (generalized Born model) and ff99SB force field, Structure calculation with CNS software, in vacuum
NMR representativeSelection criteria: best procheck statistics
NMR ensembleConformer selection criteria: structures with the lowest energy and the fewest restraint violations
Conformers calculated total number: 50 / Conformers submitted total number: 10

+
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