The G-domain of RalA is shown in blue (co-ordinates from our unpublished structure), with switch regions shown in green. The HVR of RalA is represented by the ribbon structure in orange. Schematic representations of the energy landscape sampled by each of these regions of the protein are shown below. The G-domain will have a global energy minimum, corresponding to the correctly folded state. Within this global minimum, there will be local minima representing both the GDP and GTP bound forms of the protein corresponding to inactive and active states of the protein respectively. Similar to that of Ras proteins, the active GTP-bound state can be further subdivided into distinct minima for states s1 (intermediate) and s2 (active) conformations. In contrast, the energy landscape sampled by the disordered HVR will be composed of multiple shallow minima separated by small energy barriers. This shallow, rugged energy landscape imbues this region with significant conformational dynamics, interactional promiscuity and sensitivity to environmental changes. Interaction with various regulatory proteins (1, green), post-translational modifications e.g. phosphorylation (2, pink) and interaction with various membrane environments (3, blue) can change the energy landscape by modifying local minima and/or energy barriers between minima, thus changing the structure and dynamics of the HVR.