What is the difference between small G proteins like Ras and GPCR proteins?

What is the difference between small G proteins like Ras and GPCR proteins?

• A. GPCRs hydrolyze GTP, Ras does not.
• B. Ras is a membrane channel, GPCR is a kinase.
• C. GPCRs are activated by ligand binding to GTP.
• D. Both are active when bound to GTP, but Ras has intrinsic GTPase activity to stop signaling.

Answer: (D)

The guiding idea is that signaling proteins often act as switches that are turned on when bound to GTP and off when they hydrolyze that GTP to GDP. Ras is a small GTPase, so when it grabs GTP it becomes active and can interact with downstream effectors to drive growth and differentiation signals. What makes Ras different is its own intrinsic GTPase activity: it can hydrolyze the bound GTP to GDP by itself, which switches Ras back to the inactive state and terminates the signal.

GPCRs, on the other hand, are receptors that respond to an outside ligand. They don’t themselves hydrolyze GTP. Instead, upon ligand binding, they promote GDP-to-GTP exchange on the associated G protein (the G alpha subunit of a heterotrimer), switching that G protein to its active, GTP-bound form. The signal is then transmitted through the G protein to downstream effectors. The receiver is thus the G protein, not the receptor, and termination of the signal comes from the G alpha subunit’s GTPase activity (often aided by regulators), not from the receptor.

So both Ras and the G protein’s active form require GTP to signal, but Ras carries intrinsic GTPase activity to shut itself off, whereas the GPCR itself serves as the activator of the G protein and does not hydrolyze GTP.