Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes.
Journal, issue, pages	Nature, Vol. 575, Issue 7783, Page 545-550, Year 2019
Publish date	Oct 3, 2019
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 /
PubMed Abstract	RAF family kinases are RAS-activated switches that initiate signalling 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 signalling 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; however, the structural basis for RAF regulation is poorly understood at present. Here we use cryo-electron microscopy to determine autoinhibited and active-state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer. The 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 occupies a central position that stabilizes this assembly, but the adjacent RAS-binding domain is poorly ordered and peripheral. The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding cysteine-rich domain 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, which drives the 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.
External links	Nature / PubMed:31581174 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.59 - 6.8 Å
Structure data	0541 6nyb EMDB-0541, PDB-6nyb: Structure of a MAPK pathway complex Method: EM (single particle) / Resolution: 4.1 Å 20550 6q0j EMDB-20550, PDB-6q0j: Structure of a MAPK pathway complex Method: EM (single particle) / Resolution: 4.9 Å 20551 6q0k EMDB-20551, PDB-6q0k: Structure of a MAPK pathway complex Method: EM (single particle) / Resolution: 6.8 Å 20552 6q0t EMDB-20552, PDB-6q0t: Structure of a MAPK pathway complex Method: EM (single particle) / Resolution: 5.7 Å PDB-6pp9: Crystal structure of BRAF:MEK1 complex Method: X-RAY DIFFRACTION / Resolution: 2.59 Å
Chemicals	ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogueYM ChemComp-ZN: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-LCJ: 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM ChemComp-CL: Unknown entry ChemComp-SO4: SULFATE ION ChemComp-GOL: GLYCEROL ChemComp-HOH*: WATER
Source	homo sapiens (human) spodoptera exigua (beet armyworm)
Keywords	TRANSFERASE / BRAF / MEK1 / Transferase/PROTEIN BINDING / Transferase-PROTEIN BINDING complex / SIGNALING PROTEIN/Transferase / SIGNALING PROTEIN-Transferase complex