+Open data
-Basic information
Entry | Database: PDB / ID: 4mne | ||||||
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Title | Crystal structure of the BRAF:MEK1 complex | ||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / RAF / MAPK / kinase domain / ATP-binding / ERK / RAS / PAK / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development / MAP-kinase scaffold activity ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / 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 / 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 / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / regulation of Golgi inheritance / spindle pole body / MAP kinase kinase kinase activity / 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 / regulation of stress-activated MAPK cascade / positive regulation of axonogenesis / Frs2-mediated activation / ERBB2-ERBB3 signaling pathway / stress fiber assembly / protein kinase activator activity / positive regulation of axon regeneration / endodermal cell differentiation / MAPK3 (ERK1) activation / face development / synaptic vesicle exocytosis / somatic stem cell population maintenance / MAP kinase kinase activity / Bergmann glial cell differentiation / thyroid gland development / Uptake and function of anthrax toxins / negative regulation of endothelial cell apoptotic process / Schwann cell development / positive regulation of substrate adhesion-dependent cell spreading / keratinocyte differentiation / Signal transduction by L1 / positive regulation of stress fiber assembly / response to cAMP / cellular response to calcium ion / ERK1 and ERK2 cascade / protein serine/threonine/tyrosine kinase activity / myelination / substrate adhesion-dependent cell spreading / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / insulin-like growth factor receptor signaling pathway / cellular response to nerve growth factor stimulus / thymus development / epidermal growth factor receptor signaling pathway / cell motility / long-term synaptic potentiation / animal organ morphogenesis / RAF activation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / positive regulation of protein serine/threonine kinase activity / cellular senescence / neuron differentiation / response to peptide hormone / cellular response to xenobiotic stimulus / 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 / chemotaxis / positive regulation of peptidyl-serine phosphorylation / MAPK cascade / Signaling by BRAF and RAF1 fusions / late endosome / presynapse / heart development / T cell receptor signaling pathway / regulation of cell population proliferation / protein tyrosine kinase activity / cell body / T cell differentiation in thymus / scaffold protein binding / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / early endosome / non-specific serine/threonine protein kinase Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8483 Å | ||||||
Authors | Sudhamsu, J. / Haling, J.R. / Morales, T. / Brandhuber, B. / Hymowitz, S.G. | ||||||
Citation | Journal: Cancer Cell / Year: 2014 Title: Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling. Authors: Haling, J.R. / Sudhamsu, J. / Yen, I. / Sideris, S. / Sandoval, W. / Phung, W. / Bravo, B.J. / Giannetti, A.M. / Peck, A. / Masselot, A. / Morales, T. / Smith, D. / Brandhuber, B.J. / Hymowitz, S.G. / Malek, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4mne.cif.gz | 458.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4mne.ent.gz | 365 KB | Display | PDB format |
PDBx/mmJSON format | 4mne.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4mne_validation.pdf.gz | 2.8 MB | Display | wwPDB validaton report |
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Full document | 4mne_full_validation.pdf.gz | 2.7 MB | Display | |
Data in XML | 4mne_validation.xml.gz | 77.8 KB | Display | |
Data in CIF | 4mne_validation.cif.gz | 104.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mn/4mne ftp://data.pdbj.org/pub/pdb/validation_reports/mn/4mne | HTTPS FTP |
-Related structure data
Related structure data | 4mnfC 3pp1S 3q4cS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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-Components
-Protein , 2 types, 8 molecules ADEHBCFG
#1: Protein | Mass: 37930.609 Da / Num. of mol.: 4 / Fragment: UNP residues 62-393 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 DE3 References: UniProt: Q02750, mitogen-activated protein kinase kinase #2: Protein | Mass: 35346.812 Da / Num. of mol.: 4 / Fragment: kinase domain (UNP residues 432-726) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRAF, BRAF1, RAFB1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P15056, non-specific serine/threonine protein kinase |
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-Non-polymers , 5 types, 135 molecules
#3: Chemical | ChemComp-ACP / #4: Chemical | ChemComp-MG / #5: Chemical | ChemComp-573 / #6: Chemical | ChemComp-CL / | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.89 Å3/Da / Density % sol: 57.42 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 20% PEG8000, 0.1 M Tris, pH 8.5, VAPOR DIFFUSION, HANGING DROP, temperature 292K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.98 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 24, 2012 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.8483→39.59 Å / Num. all: 79897 / Num. obs: 79897 / % possible obs: 99.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.7 % / Rsym value: 0.113 / Net I/σ(I): 13.5 |
Reflection shell | Resolution: 2.8483→3 Å / Redundancy: 6.9 % / Mean I/σ(I) obs: 2.8 / Rsym value: 0.721 / % possible all: 98.5 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRIES 3PP1 AND 3Q4C Resolution: 2.8483→39.586 Å / SU ML: 0.4 / σ(F): 1.34 / σ(I): 2.8 / Phase error: 25.88 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.8483→39.586 Å
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Refine LS restraints |
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LS refinement shell |
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