[English] 日本語
Yorodumi
- EMDB-20551: Structure of a MAPK pathway complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-20551
TitleStructure of a MAPK pathway complex
Map data
SampleERK pathway complexMAPK/ERK pathway:
Serine/threonine-protein kinase B-raf / 14-3-3 protein zeta/delta
Function / homology
Function and homology information


Translocation of SLC2A4 (GLUT4) to the plasma membrane / Activation of BAD and translocation to mitochondria / ARMS-mediated activation / Frs2-mediated activation / Spry regulation of FGF signaling / TP53 Regulates Metabolic Genes / Interleukin-3, Interleukin-5 and GM-CSF signaling / RAF activation / KSRP (KHSRP) binds and destabilizes mRNA / MAP2K and MAPK activation ...Translocation of SLC2A4 (GLUT4) to the plasma membrane / Activation of BAD and translocation to mitochondria / ARMS-mediated activation / Frs2-mediated activation / Spry regulation of FGF signaling / TP53 Regulates Metabolic Genes / Interleukin-3, Interleukin-5 and GM-CSF signaling / RAF activation / KSRP (KHSRP) binds and destabilizes mRNA / MAP2K and MAPK activation / Negative feedback regulation of MAPK pathway / GP1b-IX-V activation signalling / Negative regulation of MAPK pathway / Signaling by moderate kinase activity BRAF mutants / Signaling by high-kinase activity BRAF mutants / Signaling by RAS mutants / Signaling by BRAF and RAF fusions / Rap1 signalling / Paradoxical activation of RAF signaling by kinase inactive BRAF / Deactivation of the beta-catenin transactivating complex / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / NOTCH4 Activation and Transmission of Signal to the Nucleus / Negative regulation of NOTCH4 signaling / Signalling to p38 via RIT and RIN / Regulation of localization of FOXO transcription factors / RHO GTPases activate PKNs / regulation of synapse maturation / synaptic target recognition / Golgi reassembly / trehalose metabolism in response to stress / establishment of Golgi localization / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / protein targeting / positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway / cellular response to calcium ion / hippocampal mossy fiber to CA3 synapse / animal organ morphogenesis / melanosome / regulation of mRNA stability / membrane organization / platelet activation / ion channel binding / positive regulation of peptidyl-serine phosphorylation / vesicle / blood microparticle / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / MAPK cascade / cadherin binding / protein kinase activity / intracellular membrane-bounded organelle / glutamatergic synapse / cytokine-mediated signaling pathway / focal adhesion / transcription factor binding / protein domain specific binding / ubiquitin protein ligase binding / protein serine/threonine kinase activity / positive regulation of gene expression / protein phosphorylation / calcium ion binding / protein kinase binding / negative regulation of apoptotic process / signal transduction / mitochondrion / RNA binding / extracellular space / extracellular exosome / nucleoplasm / ATP binding / identical protein binding / plasma membrane / nucleus / cytosol / cytoplasm
Protein kinase domain / Protein kinase, ATP binding site / Protein kinase domain profile. / Ras-binding domain (RBD) profile. / 14-3-3 protein / Zinc finger phorbol-ester/DAG-type profile. / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / Raf-like Ras-binding / Serine/threonine-protein kinase, active site ...Protein kinase domain / Protein kinase, ATP binding site / Protein kinase domain profile. / Ras-binding domain (RBD) profile. / 14-3-3 protein / Zinc finger phorbol-ester/DAG-type profile. / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / Raf-like Ras-binding / Serine/threonine-protein kinase, active site / Protein kinase-like domain superfamily / Diacylglycerol/phorbol-ester binding / 14-3-3 protein, conserved site / 14-3-3 domain / Ubiquitin-like domain superfamily / 14-3-3 domain superfamily / Phorbol esters/diacylglycerol binding domain (C1 domain) / 14-3-3 protein / Raf-like Ras-binding domain / Protein tyrosine kinase / Protein kinases ATP-binding region signature. / Serine/Threonine protein kinases active-site signature. / Zinc finger phorbol-ester/DAG-type signature. / 14-3-3 proteins signature 1. / 14-3-3 proteins signature 2.
Serine/threonine-protein kinase B-raf / 14-3-3 protein zeta/delta
Biological speciesHomo sapiens (human) / Human (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.8 Å
AuthorsPark E / Rawson S / Jeon H / Eck MJ
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research InstituteP50CA165962 United States
National Institutes of Health/National Cancer InstituteR50CA221830 United States
CitationJournal: Nature / Year: 2019
Title: Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes.
Authors: Eunyoung Park / Shaun Rawson / Kunhua Li / Byeong-Won Kim / Scott B Ficarro / Gonzalo Gonzalez-Del Pino / Humayun Sharif / Jarrod A Marto / Hyesung Jeon / Michael J Eck /
Abstract: RAF family kinases are RAS-activated switches that initiate signaling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly ...RAF family kinases are RAS-activated switches that initiate signaling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly regulated, and inappropriate activation is a frequent cause of cancer. At present, the structural basis of RAF regulation is poorly understood. Here we describe autoinhibited and active state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer, determined using cryo-electron microscopy (cryo-EM). A 4.1 Å resolution cryo-EM reconstruction reveals an inactive BRAF-MEK1 complex restrained in a cradle formed by the 14-3-3 dimer, which binds the phosphorylated S365 and S729 sites that flank the BRAF kinase domain. The BRAF cysteine-rich domain (CRD) occupies a central position that stabilizes this assembly, but the adjacent RAS-binding domain (RBD) is poorly ordered and peripheral. The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding CRD and blocking dimerization of the BRAF kinase domain. In the active state, these inhibitory interactions are released and a single 14-3-3 dimer rearranges to bridge the C-terminal pS729 binding sites of two BRAFs, driving formation of an active, back-to-back BRAF dimer. Our structural snapshots provide a foundation for understanding normal RAF regulation and its mutational disruption in cancer and developmental syndromes.
Validation ReportPDB-ID: 6q0k

SummaryFull reportAbout validation report
History
DepositionAug 1, 2019-
Header (metadata) releaseOct 2, 2019-
Map releaseOct 9, 2019-
UpdateOct 9, 2019-
Current statusOct 9, 2019Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: : PDB-6q0k
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_20551.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 256 pix.
= 217.6 Å
0.85 Å/pix.
x 256 pix.
= 217.6 Å
0.85 Å/pix.
x 256 pix.
= 217.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density
Contour LevelBy AUTHOR: 0.021 / Movie #1: 0.021
Minimum - Maximum-0.037883114 - 0.12774667
Average (Standard dev.)0.00048250504 (±0.004253514)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 217.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.850.850.85
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z217.600217.600217.600
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-0.0380.1280.000

-
Supplemental data

-
Sample components

-
Entire ERK pathway complex

EntireName: ERK pathway complexMAPK/ERK pathway / Number of components: 3

-
Component #1: protein, ERK pathway complex

ProteinName: ERK pathway complexMAPK/ERK pathway / Recombinant expression: No
MassExperimental: 233 MDa
SourceSpecies: Homo sapiens (human)

-
Component #2: protein, Serine/threonine-protein kinase B-raf

ProteinName: Serine/threonine-protein kinase B-raf / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 89.322812 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

-
Component #3: protein, 14-3-3 protein zeta/delta

ProteinName: 14-3-3 protein zeta/delta / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 27.777092 kDa
SourceSpecies: Human (human)

-
Experimental details

-
Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionpH: 7.5
Support filmunspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 60 e/Å2 / Illumination mode: OTHER
LensImaging mode: OTHER
Specimen HolderModel: OTHER
CameraDetector: OTHER

-
Image processing

ProcessingMethod: single particle reconstruction / Number of projections: 66215
3D reconstructionResolution: 6.8 Å / Resolution method: FSC 0.143 CUT-OFF

-
Atomic model buiding

Modeling #1Refinement protocol: rigid body / Refinement space: REAL
Input PDB model: 4MNE, 4MNE, 3NKX, 3NKX
Chain ID: A, B, X, Y
Output model

+
About Yorodumi

-
News

-
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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
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.

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