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	BRAF oncogenic mutants evade autoinhibition through a common mechanism.
Journal, issue, pages	Science, Vol. 388, Issue 6750, Page eadp2742, Year 2025
Publish date	May 29, 2025
Authors	Hugo Lavoie / Ting Jin / Driss Lajoie / Marion Decossas / Patrick Gendron / Bing Wang / Frantisek Filandr / Malha Sahmi / Chang Hwa Jo / Sandra Weber / Geneviève Arseneault / Sasmita Tripathy / Pierre Beaulieu / Doris A Schuetz / David C Schriemer / Anne Marinier / William J Rice / Pierre Maisonneuve / Marc Therrien /
PubMed Abstract	Uncontrolled activation of the rat sarcoma (RAS)-extracellular signal-regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving ...Uncontrolled activation of the rat sarcoma (RAS)-extracellular signal-regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain unclear. By using cryo-electron microscopy, we solved the three-dimensional structures of the three oncogenic BRAF mutant classes, including the common V600E variant. These mutations disrupted wild-type BRAF's autoinhibited state, mediated by interactions between the cysteine-rich domain and kinase domain, thereby shifting the kinase domain into a preactivated conformation. This structural change likely results from helix αC displacement. PLX8394, a BRAF inhibitor that stabilizes helix αC in an inactive conformation, restored the autoinhibited conformation of oncogenic BRAF, explaining the properties of this class of compounds.
External links	Science / PubMed:40440367
Methods	EM (single particle)
Resolution	3.06 - 5.86 Å
Structure data	43673 8vyo EMDB-43673, PDB-8vyo: Cryo-EM Structure of the BRAF WT monomer Method: EM (single particle) / Resolution: 3.74 Å 43674 8vyp EMDB-43674, PDB-8vyp: Cryo-EM Structure of the BRAF V600E monomer Method: EM (single particle) / Resolution: 3.29 Å 43675 8vyq EMDB-43675, PDB-8vyq: Cryo-EM Structure of the BRAF V600K monomer Method: EM (single particle) / Resolution: 4.43 Å 43676 8vyr EMDB-43676, PDB-8vyr: Cryo-EM Structure of the BRAF V600E monomer bound to GDC0879 Method: EM (single particle) / Resolution: 4.32 Å 43677 8vys EMDB-43677, PDB-8vys: Cryo-EM Structure of the BRAF V600E monomer bound to PLX8394 Method: EM (single particle) / Resolution: 3.06 Å 43678 8vyu EMDB-43678, PDB-8vyu: Cryo-EM Structure of the BRAF WT monomer bound to PLX8394 Method: EM (single particle) / Resolution: 4.07 Å 43679 8vyv EMDB-43679, PDB-8vyv: Cryo-EM Structure of the BRAF K601E monomer Method: EM (single particle) / Resolution: 5.86 Å 43680 8vyw EMDB-43680, PDB-8vyw: Cryo-EM Structure of the BRAF D594G monomer Method: EM (single particle) / Resolution: 4.76 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogueYM PDB-1aen*: SPECIFICITY OF LIGAND BINDING TO A BURIED POLAR CAVITY AT THE ACTIVE SITE OF CYTOCHROME C PEROXIDASE (2-AMINO-5-METHYLTHIAZOLE)
Source	homo sapiens (human)
Keywords	TRANSFERASE/INHIBITOR / BRAF Kinase Monomer / TRANSFERASE-INHIBITOR complex / BRAF Kinase Oncogenic Mutant Monomer / BRAF Kinase Monomer Mutant Inhibitor / BRAF Kinase Monomer Inhibitor