Ras GTPase cycle. Ras interconverts between active GTP-bound state (Ras-GTP) and inactive GDP-bound state (Ras-GDP). Ras regulatory proteins, known as SOS and GAP, facilitate the transformation between the two states. The most significant conformational differences between GDP-bound Ras and GTP-bound Ras are located at the nucleotide binding pocket, consisting of P-loop (lime), switch I (pink) and switch II (light blue) regions. In the GDP-bound state, the pocket is ‘open’, while in the GTP-bound state, it is ‘closed’. The GTP-bound Ras has higher affinity towards effector proteins (e.g., Raf), which keeps Ras signaling in the ‘ON’ state. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)