[English] 日本語
Yorodumi
- PDB-8s42: Ternary structure of 14-3-3s, C-RAF phosphopeptide (pS259) and co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8s42
TitleTernary structure of 14-3-3s, C-RAF phosphopeptide (pS259) and compound 80 (1124898)
Components
  • 14-3-3 protein sigma
  • RAF proto-oncogene serine/threonine-protein kinase
KeywordsPEPTIDE BINDING PROTEIN / Stabilizer / protein-protein interaction
Function / homology
Function and homology information


death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / insulin secretion involved in cellular response to glucose stimulus / Negative feedback regulation of MAPK pathway / IFNG signaling activates MAPKs ...death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / insulin secretion involved in cellular response to glucose stimulus / Negative feedback regulation of MAPK pathway / IFNG signaling activates MAPKs / GP1b-IX-V activation signalling / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / ERBB2-ERBB3 signaling pathway / keratinization / regulation of cell-cell adhesion / face development / pseudopodium / regulation of cell differentiation / neurotrophin TRK receptor signaling pathway / thyroid gland development / cAMP/PKA signal transduction / somatic stem cell population maintenance / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / extrinsic apoptotic signaling pathway via death domain receptors / phosphoserine residue binding / MAP kinase kinase kinase activity / Activation of BAD and translocation to mitochondria / type II interferon-mediated signaling pathway / negative regulation of keratinocyte proliferation / establishment of skin barrier / negative regulation of protein localization to plasma membrane / negative regulation of protein-containing complex assembly / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Schwann cell development / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of stem cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / activation of adenylate cyclase activity / positive regulation of peptidyl-serine phosphorylation / positive regulation of protein localization / response to muscle stretch / myelination / CD209 (DC-SIGN) signaling / positive regulation of cell adhesion / protein sequestering activity / insulin-like growth factor receptor signaling pathway / negative regulation of innate immune response / protein export from nucleus / release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / thymus development / positive regulation of protein export from nucleus / negative regulation of protein kinase activity / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / RAF activation / wound healing / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / Stimuli-sensing channels / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by RAF1 mutants / Negative regulation of MAPK pathway / 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 / MAPK cascade / protein localization / insulin receptor signaling pathway / regulation of protein localization / positive regulation of cell growth / regulation of apoptotic process / mitochondrial outer membrane / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity
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 / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / 14-3-3 protein sigma / Zinc finger phorbol-ester/DAG-type profile. ...Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / 14-3-3 protein sigma / 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 / Ubiquitin-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / 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
Similarity search - Domain/homology
: / RAF proto-oncogene serine/threonine-protein kinase / 14-3-3 protein sigma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å
AuthorsKonstantinidou, M. / Vickery, H. / Pennings, M.A.M. / Virta, J. / Visser, E.J. / Oetelaar, M.C.M. / Overmans, M. / Neitz, J. / Ottmann, C. / Brunsveld, L. / Arkin, M.R.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM147696 United States
CitationJournal: To Be Published
Title: Small molecule stabilization of the 14-3-3sigma/CRAF complex inhibits the MAPK pathway
Authors: Konstantinidou, M. / Vickery, H. / Pennings, M.A.M. / Virta, J. / Visser, E.J. / Oetelaar, M.C.M. / Overmans, M. / Neitz, J. / Ottmann, C. / Brunsveld, L. / Arkin, M.R.
History
DepositionFeb 21, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 5, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: 14-3-3 protein sigma
P: RAF proto-oncogene serine/threonine-protein kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,1286
Polymers27,6132
Non-polymers5154
Water5,477304
1
B: 14-3-3 protein sigma
P: RAF proto-oncogene serine/threonine-protein kinase
hetero molecules

B: 14-3-3 protein sigma
P: RAF proto-oncogene serine/threonine-protein kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,25612
Polymers55,2264
Non-polymers1,0308
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Buried area5540 Å2
ΔGint-70 kcal/mol
Surface area22850 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.701, 112.302, 63.094
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules BP

#1: Protein 14-3-3 protein sigma / Epithelial cell marker protein 1 / Stratifin


Mass: 26542.914 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947
#2: Protein/peptide RAF proto-oncogene serine/threonine-protein kinase / Proto-oncogene c-RAF / cRaf / Raf-1


Mass: 1070.028 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
References: UniProt: P04049, non-specific serine/threonine protein kinase

-
Non-polymers , 4 types, 308 molecules

#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-A1H5F / 2-chloranyl-1-[8-[3-fluoranyl-4-(trifluoromethyl)phenyl]sulfonyl-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl]ethanone


Mass: 430.802 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H15ClF4N2O4S / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 304 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.62 Å3/Da / Density % sol: 53.06 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.095 M HEPES pH=7.1-7.7 0.19 M CaCl2 5% glycerol 24-29% PEG400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.885603 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 30, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.885603 Å / Relative weight: 1
ReflectionResolution: 1.7→45.63 Å / Num. obs: 32215 / % possible obs: 99.8 % / Redundancy: 13.1 % / CC1/2: 0.998 / Net I/σ(I): 13.6
Reflection shellResolution: 1.7→1.73 Å / Mean I/σ(I) obs: 2.2 / Num. unique obs: 1676 / CC1/2: 0.786

-
Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
autoPROCdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.7→45.63 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 18.55 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.1936 1591 4.94 %RANDOM
Rwork0.174 ---
obs0.175 32194 99.7 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.7→45.63 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1881 0 35 304 2220
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.007449
X-RAY DIFFRACTIONf_angle_d0.901470
X-RAY DIFFRACTIONf_dihedral_angle_d9.013279
X-RAY DIFFRACTIONf_chiral_restr0.049290
X-RAY DIFFRACTIONf_plane_restr0.008334
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.7-1.750.25711320.23422750X-RAY DIFFRACTION100
1.75-1.820.21611510.20392733X-RAY DIFFRACTION100
1.82-1.890.2191590.19932717X-RAY DIFFRACTION100
1.89-1.980.24041380.19182775X-RAY DIFFRACTION100
1.98-2.080.19751520.17112744X-RAY DIFFRACTION100
2.08-2.210.18461570.16172737X-RAY DIFFRACTION99
2.21-2.380.16551300.16032757X-RAY DIFFRACTION99
2.38-2.620.19581330.16972805X-RAY DIFFRACTION100
2.62-30.20831440.17812806X-RAY DIFFRACTION100
3-3.780.19251450.16992837X-RAY DIFFRACTION100
3.78-45.630.17471500.16832942X-RAY DIFFRACTION100
Refinement TLS params.Method: refined / Origin x: -17.6497 Å / Origin y: 17.1399 Å / Origin z: 7.6225 Å
111213212223313233
T0.1242 Å20.0103 Å2-0.0013 Å2-0.1455 Å2-0.0103 Å2--0.1405 Å2
L0.4468 °2-0.2791 °2-0.1777 °2-0.7597 °20.1385 °2--0.6155 °2
S-0.0008 Å °-0.0137 Å °0.0196 Å °0.0111 Å °0.0182 Å °0.0525 Å °-0.022 Å °-0.0715 Å °0.0001 Å °
Refinement TLS groupSelection details: all

+
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