G-Protein Coupled Receptors Overview

G-protein Coupled Receptor (GPCR)

• GPCRs are membrane-bound proteins that bind to signaling molecules, initiating a cascade of events within the cell.
• The binding of an extracellular signaling molecule causes a conformational change in the GPCR, allowing it to activate a GTP-binding protein (G-protein).
• These receptors thread through the cell membrane seven times, with the N-terminus located outside the cell and the C-terminus inside the cell.

G-Protein Structure and Activation

• G-proteins are heterotrimeric, meaning they consist of three subunits: alpha, beta, and gamma.
• In their inactive state, G-proteins have GDP bound to the alpha subunit.
• Upon signal molecule binding to the GPCR, the alpha subunit's affinity for GDP decreases, allowing GTP to bind in its place.
• This binding event causes the alpha subunit to detach from the beta and gamma subunits, activating the G-protein.
• Activated alpha and beta/gamma subunits interact with target proteins, such as enzymes or ion channels, to trigger cellular responses.

G-Protein Deactivation and Regulation

• The alpha subunit possesses GTPase activity, meaning it can hydrolyze GTP back to GDP.
• This GTP hydrolysis returns the alpha subunit to its inactive conformation, allowing it to reassociate with the beta/gamma subunits.
• GTPase activity is enhanced by the binding of the alpha subunit to target proteins or RGS proteins.
• RGS proteins are specific regulators of G-protein signaling and act as GTPase activating proteins (GAPs), accelerating the GTP hydrolysis process.
• This rapid deactivation of G-proteins ensures a precise and controlled cellular response.