Figure 8.

Proposed energetic model for Eph activation by the juxtamembrane and SAM domain linker. The initial step of Eph activation occurs with the displacement of the juxtamembrane from its autoinhibitory conformation. Displacement of the autoinhibitory conformation occurs with an increase in entropy and is facilitated by 1) autophosphorylation of the juxtamembrane and/or 2) untethering of the SAM domain linker. This allows for further autophosphorylation to occur (i.e. autophosphorylation on the activation loop shown in red) to complete the activation process. SAM domain network mutants affect the dynamics of the autoinhibitory juxtamembrane, altering the activation energy required for activation.