Fig. 3: The allosteric binders Nb14, Nb22 and RASY64A impact the SOS1-RAS nucleotide exchange cycle by different mechanisms.
From: Allosteric nanobodies to study the interactions between SOS1 and RAS
a Minimal four-step mechanism describing the SOS1-catalyzed nucleotide exchange cycle of RAS including the formation of the transition state RAS•GDP•SOS1 (top) followed by nucleotide dissociation and accumulation of the more stable RAS•SOS1 complex. The cycle is completed by the binding of GTP to form RAS•GTP•SOS1, and the subsequent release of SOS1, causing the accumulation of RAS•GTP. Because of the symmetry of this cycle, we only determined the kinetic parameters of the boxed part. b Effects of the allosteric nanobodies and allosteric RAS on the kinetics of the SOS catalyzed nucleotide exchange reaction. c Kinetic map to visually compare the effects of the different allosteric modulators on the nucleotide exchange kinetics and equilibria.
