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- PDB-7mfd: Autoinhibited BRAF:(14-3-3)2:MEK complex with the BRAF RBD resolved -
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Open data
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Basic information
Entry | Database: PDB / ID: 7mfd | |||||||||
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Title | Autoinhibited BRAF:(14-3-3)2:MEK complex with the BRAF RBD resolved | |||||||||
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![]() | SIGNALING PROTEIN/TRANSFERASE / B-Raf / MEK / 14-3-3 / B-Raf complex / B-Raf monomer / Inactive B-Raf / Serine/threonine-protein kinase B-raf / RBD / signaling protein / SIGNALING PROTEIN-TRANSFERASE complex | |||||||||
Function / homology | ![]() Golgi reassembly / synaptic target recognition / epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / respiratory system process / NOTCH4 Activation and Transmission of Signal to the Nucleus / regulation of synapse maturation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / trehalose metabolism in response to stress ...Golgi reassembly / synaptic target recognition / epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / respiratory system process / NOTCH4 Activation and Transmission of Signal to the Nucleus / regulation of synapse maturation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / trehalose metabolism in response to stress / regulation of axon regeneration / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / mitogen-activated protein kinase kinase / establishment of Golgi localization / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development / MAP-kinase scaffold activity / type B pancreatic cell proliferation / Signalling to p38 via RIT and RIN / cerebellar cortex formation / head morphogenesis / myeloid progenitor cell differentiation / tube formation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / Signaling by MAP2K mutants / Rap1 signalling / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / negative regulation of protein localization to nucleus / regulation of Golgi inheritance / mitogen-activated protein kinase kinase binding / trachea formation / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / KSRP (KHSRP) binds and destabilizes mRNA / positive regulation of axonogenesis / regulation of stress-activated MAPK cascade / Frs2-mediated activation / GP1b-IX-V activation signalling / ERBB2-ERBB3 signaling pathway / stress fiber assembly / positive regulation of axon regeneration / protein kinase activator activity / endodermal cell differentiation / face development / MAPK3 (ERK1) activation / synaptic vesicle exocytosis / somatic stem cell population maintenance / Bergmann glial cell differentiation / MAP kinase kinase activity / thyroid gland development / Uptake and function of anthrax toxins / Regulation of localization of FOXO transcription factors / Interleukin-3, Interleukin-5 and GM-CSF signaling / phosphoserine residue binding / MAP kinase kinase kinase activity / Activation of BAD and translocation to mitochondria / protein targeting / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / cellular response to glucose starvation / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Schwann cell development / negative regulation of endothelial cell apoptotic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / positive regulation of substrate adhesion-dependent cell spreading / RHO GTPases activate PKNs / keratinocyte differentiation / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / response to cAMP / protein sequestering activity / cellular response to calcium ion / ERK1 and ERK2 cascade / negative regulation of innate immune response / protein serine/threonine/tyrosine kinase activity / myelination / hippocampal mossy fiber to CA3 synapse / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / substrate adhesion-dependent cell spreading / regulation of ERK1 and ERK2 cascade / insulin-like growth factor receptor signaling pathway / cellular response to nerve growth factor stimulus / thymus development / Signal transduction by L1 / Translocation of SLC2A4 (GLUT4) to the plasma membrane / Deactivation of the beta-catenin transactivating complex / cell motility / long-term synaptic potentiation / TP53 Regulates Metabolic Genes / animal organ morphogenesis / Negative regulation of NOTCH4 signaling / RAF activation / Spry regulation of FGF signaling / lung development Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.66 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. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 217.3 KB | Display | ![]() |
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PDB format | ![]() | 173.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 839.8 KB | Display | ![]() |
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Full document | ![]() | 864.1 KB | Display | |
Data in XML | ![]() | 41.9 KB | Display | |
Data in CIF | ![]() | 62.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23813MC ![]() 7mfeC ![]() 7mffC 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: 84697.695 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P15056, non-specific serine/threonine protein kinase | ||||||
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#2: Protein | Mass: 43493.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: Q02750, mitogen-activated protein kinase kinase | ||||||
#3: Protein | Mass: 27777.092 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #4: Chemical | #5: Chemical | ChemComp-CHU / | Has ligand of interest | N | |
-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
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Details: 20mAmp / Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||
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: 3.66 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142852 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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