The mechanism of Raf activation through dimerization
Mingzhen Zhang, Ryan Maloney, Hyunbum Jang, Ruth Nussinov
Abstract
-autophosphorylation. Once fully activated, the ON-state kinase domain can be stabilized by a newly identified functional N-terminal basic (NtB) motif in the dimer for Raf signaling. This work provides atomic level insight into critical steps in Raf activation and outlines a new venue for drug discovery against Raf dimerization.
Topics & Concepts
AutophosphorylationDimerProtein kinase domainChemistryKinaseStackingPhosphorylationSerineCell biologyMAPK/ERK pathwaySignal transductionProtein kinase AEnzyme activatorStereochemistryBiochemistryBiophysicsBiologyMutantOrganic chemistryGeneMelanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingComputational Drug Discovery Methods