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Open data
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Basic information
Entry | Database: PDB / ID: 7mff | |||||||||
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Title | Dimeric (BRAF)2:(14-3-3)2 complex bound to SB590885 Inhibitor | |||||||||
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![]() | SIGNALING PROTEIN / B-Raf / 14-3-3 / B-Raf complex / B-Raf dimer / Active B-Raf / SB590885 / Serine/threonine-protein kinase B-raf | |||||||||
Function / homology | ![]() synaptic target recognition / Golgi reassembly / CD4-positive, alpha-beta T cell differentiation / positive regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / 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 / CD4-positive, alpha-beta T cell differentiation / positive regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / 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 / myeloid progenitor cell differentiation / endothelial cell apoptotic process / regulation of synapse maturation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / positive regulation of D-glucose transmembrane transport / negative regulation of fibroblast migration / 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 / mitogen-activated protein kinase kinase binding / GP1b-IX-V activation signalling / Frs2-mediated activation / stress fiber assembly / face development / MAP kinase kinase activity / synaptic vesicle exocytosis / thyroid gland development / Regulation of localization of FOXO transcription factors / Interleukin-3, Interleukin-5 and GM-CSF signaling / somatic stem cell population maintenance / phosphoserine residue binding / positive regulation of peptidyl-serine phosphorylation / MAP kinase kinase kinase activity / Activation of BAD and translocation to mitochondria / postsynaptic modulation of chemical synaptic transmission / protein targeting / negative regulation of endothelial cell apoptotic process / regulation of ERK1 and ERK2 cascade / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / response to cAMP / 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 / cellular response to calcium ion / protein sequestering activity / negative regulation of innate immune response / hippocampal mossy fiber to CA3 synapse / thymus development / animal organ morphogenesis / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H2AS121 kinase activity / histone H3S57 kinase activity / histone H3S28 kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / ribosomal protein S6 kinase activity / histone H2AT120 kinase activity / eukaryotic translation initiation factor 2alpha kinase activity / histone H2BS36 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H3S10 kinase activity / AMP-activated protein kinase activity / histone H3T11 kinase activity / histone H3T3 kinase activity / 3-phosphoinositide-dependent protein kinase activity / Translocation of SLC2A4 (GLUT4) to the plasma membrane / histone H3T45 kinase activity / TP53 Regulates Metabolic Genes / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / Deactivation of the beta-catenin transactivating complex / lung development / RAF activation / cellular response to nerve growth factor stimulus / 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 / response to peptide hormone / centriolar satellite / long-term synaptic potentiation / epidermal growth factor receptor signaling pathway Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.89 Å | |||||||||
![]() | Martinez Fiesco, J.A. / Ping, Z. / Durrant, D.E. / Morrison, D.K. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding. Authors: Juliana A Martinez Fiesco / David E Durrant / Deborah K Morrison / Ping Zhang / ![]() Abstract: RAF kinases are essential effectors of RAS, but how RAS binding initiates the conformational changes needed for autoinhibited RAF monomers to form active dimers has remained unclear. Here, we present ...RAF kinases are essential effectors of RAS, but how RAS binding initiates the conformational changes needed for autoinhibited RAF monomers to form active dimers has remained unclear. Here, we present cryo-electron microscopy structures of full-length BRAF complexes derived from mammalian cells: autoinhibited, monomeric BRAF:14-3-3:MEK and BRAF:14-3-3 complexes, and an inhibitor-bound, dimeric BRAF:14-3-3 complex, at 3.7, 4.1, and 3.9 Å resolution, respectively. In both autoinhibited, monomeric structures, the RAS binding domain (RBD) of BRAF is resolved, revealing that the RBD forms an extensive contact interface with the 14-3-3 protomer bound to the BRAF C-terminal site and that key basic residues required for RBD-RAS binding are exposed. Moreover, through structure-guided mutational studies, our findings indicate that RAS-RAF binding is a dynamic process and that RBD residues at the center of the RBD:14-3-3 interface have a dual function, first contributing to RAF autoinhibition and then to the full spectrum of RAS-RBD interactions. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 201.8 KB | Display | ![]() |
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PDB format | ![]() | 151.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 926.8 KB | Display | ![]() |
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Full document | ![]() | 938.7 KB | Display | |
Data in XML | ![]() | 34.8 KB | Display | |
Data in CIF | ![]() | 51.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23815MC ![]() 7mfdC ![]() 7mfeC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 27777.092 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 84697.695 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P15056, non-specific serine/threonine protein kinase #3: Chemical | Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Active dimeric (B-Raf)2:(14-3-3)2 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT | ||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 277.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 57 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.89 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 203343 / Symmetry type: POINT | ||||||||||||||||||||||||
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