Transmembrane Receptors That Activate G Proteins
- GPCRs are a large family of transmembrane receptors found in the plasma membrane of cells.
- They are called "G protein-coupled" because they work in partnership with G proteins, molecular switches that relay signals inside the cell.
Definition
G protein-coupled receptors
A large family of transmembrane receptors that detect external signals and activate intracellular G proteins, initiating cellular responses.
Structure of GPCRs
- Seven-Helix Structure: GPCRs span the membrane with seven alpha-helices.
- Ligand-Binding Site: Located on the extracellular side, where signaling molecules (ligands) bind.
- Intracellular Domain: Interacts with G proteins to transmit the signal into the cell.
- Think of a GPCR as a doorbell.
- The ligand is the person pressing the button, the receptor is the bell, and the G protein is the wiring that carries the signal to the chime inside the house.
How Do GPCRs Work?
1. Ligand Binding
The process begins when a ligand - such as a hormone, neurotransmitter, or sensory molecule - binds to the receptor’s extracellular site.
ExampleEpinephrine (adrenaline) binds to its receptor on liver cells to trigger the release of glucose into the bloodstream.
2. Activation of the G Protein
- Inactive State: The G protein is bound to guanosine diphosphate (GDP) and is inactive.
- Conformational Change: Ligand binding causes the GPCR to change shape, activating the G protein.
- GDP to GTP Exchange: The alpha subunit of the G protein releases GDP and binds guanosine triphosphate (GTP), activating the G protein.
- Don’t confuse GDP and GTP with ATP.
- While ATP is the cell’s main energy currency, GTP specifically activates G proteins.
3. Signal Propagation
- Subunit Separation: The activated G protein splits into two parts: the alpha subunit (with GTP) and the beta-gamma dimer.
- Effector Activation: These subunits interact with target proteins in the membrane, such as enzymes or ion channels, to trigger the next steps in the signaling pathway.
