[English] 日本語
Yorodumi
- PDB-6u2h: BRAF dimer bound to 14-3-3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6u2h
TitleBRAF dimer bound to 14-3-3
Components
  • 14-3-3 protein zeta/delta
  • Serine/threonine-protein kinase B-raf
KeywordsSIGNALING PROTEIN/Transferase / BRAF / 14-3-3 / kinase / complex / SIGNALING PROTEIN / SIGNALING PROTEIN-Transferase complex
Function / homology
Function and homology information


synaptic target recognition / Golgi reassembly / positive regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / establishment of Golgi localization / Signalling to p38 via RIT and RIN / respiratory system process ...synaptic target recognition / Golgi reassembly / positive regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / establishment of Golgi localization / Signalling to p38 via RIT and RIN / respiratory system process / head morphogenesis / ARMS-mediated activation / tube formation / regulation of synapse maturation / endothelial cell apoptotic process / myeloid progenitor cell differentiation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / positive regulation of D-glucose transmembrane transport / negative regulation of fibroblast migration / Rap1 signalling / establishment of protein localization to membrane / positive regulation of axonogenesis / negative regulation of protein localization to nucleus / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / KSRP (KHSRP) binds and destabilizes mRNA / Frs2-mediated activation / GP1b-IX-V activation signalling / stress fiber assembly / face development / MAP kinase kinase activity / thyroid gland development / Interleukin-3, Interleukin-5 and GM-CSF signaling / Regulation of localization of FOXO transcription factors / synaptic vesicle exocytosis / somatic stem cell population maintenance / positive regulation of peptidyl-serine phosphorylation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / MAP kinase kinase kinase activity / postsynaptic modulation of chemical synaptic transmission / negative regulation of endothelial cell apoptotic process / regulation of ERK1 and ERK2 cascade / protein targeting / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / cellular response to glucose starvation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / ERK1 and ERK2 cascade / positive regulation of substrate adhesion-dependent cell spreading / Transcriptional and post-translational regulation of MITF-M expression and activity / substrate adhesion-dependent cell spreading / lung development / cellular response to calcium ion / protein sequestering activity / negative regulation of innate immune response / thymus development / hippocampal mossy fiber to CA3 synapse / animal organ morphogenesis / TP53 Regulates Metabolic Genes / Translocation of SLC2A4 (GLUT4) to the plasma membrane / Deactivation of the beta-catenin transactivating complex / RAF activation / Negative regulation of NOTCH4 signaling / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / regulation of protein stability / centriolar satellite / cellular response to xenobiotic stimulus / epidermal growth factor receptor signaling pathway / long-term synaptic potentiation / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by BRAF and RAF1 fusions / intracellular protein localization / melanosome / T cell differentiation in thymus / T cell receptor signaling pathway / presynapse / MAPK cascade / regulation of cell population proliferation / cell body / scaffold protein binding / angiogenesis / protein phosphatase binding / blood microparticle / vesicle / DNA-binding transcription factor binding / negative regulation of neuron apoptotic process / transmembrane transporter binding / positive regulation of ERK1 and ERK2 cascade
Similarity search - Function
Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / 14-3-3 domain / Delta-Endotoxin; domain 1 / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. ...Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / 14-3-3 domain / Delta-Endotoxin; domain 1 / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. / 14-3-3 protein / 14-3-3 homologues / 14-3-3 domain / 14-3-3 domain superfamily / 14-3-3 protein / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, 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 / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-29L / Serine/threonine-protein kinase B-raf / 14-3-3 protein zeta/delta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsLiau, N.P.D. / Hymowitz, S.G. / Sudhamsu, J.
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2020
Title: Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization.
Authors: Liau, N.P.D. / Wendorff, T.J. / Quinn, J.G. / Steffek, M. / Phung, W. / Liu, P. / Tang, J. / Irudayanathan, F.J. / Izadi, S. / Shaw, A.S. / Malek, S. / Hymowitz, S.G. / Sudhamsu, J.
History
DepositionAug 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 28, 2019Provider: repository / Type: Initial release
Revision 1.1Feb 5, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Feb 26, 2020Group: 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 1.3Oct 11, 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
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 14-3-3 protein zeta/delta
B: 14-3-3 protein zeta/delta
C: Serine/threonine-protein kinase B-raf
D: Serine/threonine-protein kinase B-raf
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,7646
Polymers119,0954
Non-polymers6692
Water37821
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8410 Å2
ΔGint-32 kcal/mol
Surface area46160 Å2
MethodPISA
Unit cell
Length a, b, c (Å)61.504, 115.752, 153.092
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein 14-3-3 protein zeta/delta / Protein kinase C inhibitor protein 1 / KCIP-1


Mass: 26460.891 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: YWHAZ / Production host: Escherichia coli (E. coli) / References: UniProt: P63104
#2: Protein Serine/threonine-protein kinase B-raf / Proto-oncogene B-Raf / p94 / v-Raf murine sarcoma viral oncogene homolog B1


Mass: 33086.852 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Escherichia coli (E. coli)
References: UniProt: P15056, non-specific serine/threonine protein kinase
#3: Chemical ChemComp-29L / 2-{4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridin-4-yl)-1H-pyrazol-1-yl}ethanol


Mass: 334.372 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H18N4O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 21 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.36 Å3/Da / Density % sol: 47.88 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: PEG 6000 Tris pH 7.5

-
Data collection

DiffractionMean temperature: 77 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 17, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.5→34.454 Å / Num. obs: 72587 / % possible obs: 99.26 % / Redundancy: 6.7 % / CC1/2: 0.999 / Rmerge(I) obs: 0.08109 / Net I/σ(I): 13.91
Reflection shellResolution: 2.5→2.589 Å / Rmerge(I) obs: 1.718 / Mean I/σ(I) obs: 0.88 / Num. unique obs: 26121 / CC1/2: 0.528 / % possible all: 99.27

-
Processing

Software
NameVersionClassification
PHENIX1.12-2829_finalrefinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
XDSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4MNF, 5NAS

4mnf

5nas


Resolution: 2.5→34.454 Å / SU ML: 0.44 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 32.23 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2632 2947 4.06 %
Rwork0.2197 69640 -
obs0.2215 72587 99.37 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 216.51 Å2 / Biso mean: 95.6009 Å2 / Biso min: 38.61 Å2
Refinement stepCycle: final / Resolution: 2.5→34.454 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8090 0 50 21 8161
Biso mean--75.18 76.77 -
Num. residues----1011
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0118287
X-RAY DIFFRACTIONf_angle_d1.34511159
X-RAY DIFFRACTIONf_chiral_restr0.0861214
X-RAY DIFFRACTIONf_plane_restr0.0071431
X-RAY DIFFRACTIONf_dihedral_angle_d21.1663174
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.5-2.5410.421410.3954327397
2.541-2.58480.37661410.37063317100
2.5848-2.63180.37041420.36663328100
2.6318-2.68240.37451410.34563374100
2.6824-2.73710.35521390.33883268100
2.7371-2.79660.32581410.3234331498
2.7966-2.86170.37491440.3174327199
2.8617-2.93320.37391420.30283324100
2.9332-3.01240.31091380.29673310100
3.0124-3.1010.33591450.27933356100
3.101-3.20110.36681350.2783359100
3.2011-3.31540.32241380.2663269100
3.3154-3.4480.34281380.24823369100
3.448-3.60480.26171440.24423330100
3.6048-3.79460.24431350.2177326698
3.7946-4.0320.2341420.20943330100
4.032-4.34280.22891420.1823328100
4.3428-4.77880.21771400.1683336100
4.7788-5.46790.26311390.1872330298
5.4679-6.880.21971430.20513314100
6.88-34.4540.21681370.1644330299
Refinement TLS params.Method: refined / Origin x: 65.3088 Å / Origin y: 116.2711 Å / Origin z: -16.1859 Å
111213212223313233
T0.3638 Å20.0959 Å2-0.0189 Å2-0.39 Å20.0426 Å2--0.4755 Å2
L0.5504 °20.1525 °2-0.0448 °2-0.4319 °20.1729 °2--1.1888 °2
S-0.0133 Å °0.196 Å °0.1575 Å °-0.0694 Å °0.0224 Å °0.0629 Å °0.0921 Å °-0.0415 Å °0 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA1 - 230
2X-RAY DIFFRACTION1allB0 - 229
3X-RAY DIFFRACTION1allC448 - 733
4X-RAY DIFFRACTION1allC801
5X-RAY DIFFRACTION1allD448 - 733
6X-RAY DIFFRACTION1allD801
7X-RAY DIFFRACTION1allS1 - 31

+
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