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.
In the case of epinephrine, the activated G protein stimulates adenylyl cyclase, an enzyme that converts ATP into cyclic AMP (cAMP), a secondary messenger.
4. Termination of the Signal
- Hydrolysis of GTP: The alpha subunit hydrolyzes GTP back to GDP, inactivating itself.
- Reassembly: The G protein subunits reassemble, and the system returns to its resting state, ready for the next signal.
To remember the steps, think of the acronym L-A-S-T: Ligand binding, Activation, Signal propagation, Termination.
GPCRs Are Key to Sensory Perception, Hormonal Regulation, and Neurotransmission
GPCRs are incredibly versatile and are involved in a wide range of physiological processes, including:
- Sensory Perception: Detecting light, odors, and tastes.
- Hormonal Responses: Regulating metabolism, growth, and stress responses.
- Neurotransmission: Mediating communication between neurons.
Examples of GPCRs and Their Signaling Molecules
| GPCR Type | Signaling molecule | Mechanism of Action | Response |
|---|---|---|---|
| β-Adrenergic Receptor | Epinephrine (Adrenaline) | Activates adenylyl cyclase via Gαs, increasing cAMP levels and promoting fight-or-flight responses. | Heart rate increase |
| Acetylcholine Receptor | Acetylcholine | Activates phospholipase C via Gαq, leading to IP₃ and DAG production, causing smooth muscle contraction. | Parasympathetic responses |
| Rhodopsin | Light | Activates G proteins in photoreceptor cells, triggering a visual signal cascade. | Vision in Retina |
| Histamine Receptor | Histamine | Activates G proteins to regulate inflammation and allergic responses. | Inflammatory response in tissues |
A Closer Look: The Epinephrine Pathway
- Ligand Binding: Epinephrine binds to its GPCR on the cell membrane.
- G Protein Activation: The G protein exchanges GDP for GTP and activates adenylyl cyclase.
- cAMP Production: Adenylyl cyclase converts ATP into cAMP, which acts as a secondary messenger.
- Signal Amplification: cAMP activates protein kinase A (PKA), which phosphorylates enzymes to break down glycogen into glucose.
- Rapid Response: Within seconds, glucose is released into the bloodstream, providing energy for the "fight or flight" response.
- How does the specificity of GPCRs reflect the broader principle of structure-function relationships in biology?
- Can you think of other examples where small structural changes have significant functional impacts?
- Can you outline the steps of GPCR activation and explain how the signal is terminated?
- What is the role of the Gα subunit in the signaling pathway?
