FIG 3.

Activation of Raf is initiated by the release of the inhibitory N-terminal domain. The initial step in the activation of Raf is binding of Ras(GTP) to the N-terminal domain, which “unleashes” the kinase domain. In the absence of Ras(GTP), the kinase domain is locked into an inhibited state where the R-spine is assumed to be broken and, we suspect, ATP cannot bind. Unleashing of the kinase domain allows for the dynamic toggling of the R-spine between its assembled and disassembled state, although equilibrium most likely favors the broken spine.