Fig. 6: Model for BRAF monomer to dimer transition.
From: Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding
Upon RAS activation, the autoinhibited BRAF monomer is recruited to the plasma membrane through direct ionic interactions between the BRAF RBD and the switch I region of RAS. As RAS forms the full spectrum of RBD contacts, steric clashes, and electrostatic repulsion occur between RAS and 14-3-3, resulting in conformational changes that dislodge the RBD/CRD and promote a rearrangement in 14-3-3 dimer binding, thus exposing the pS365 site and the BRAF dimer interface. The dislodged CRD rotates to interact with the membrane and RAS to further stabilize the interaction. The exposed KD can then dimerize and assume the active catalytic conformation that is stabilized by 14-3-3 dimer binding to the pS729 sites on each BRAF protomer.
