1. G Protein-Coupled Receptors
Chapter 5
G Protein-Coupled Receptors

2. You must know
The role of G protein-coupled receptors.

3. Reception, the Binding of a Signaling Molecule to a Receptor Protein
The binding between a signal molecule (ligand) and receptor is highly specific.
Ligand binding generally causes a shape change in the receptor.
Many receptors are directly activated by this shape change.
Most signal receptors are plasma membrane proteins.
© 2014 Pearson Education, Inc. 3

4. Receptors in the Plasma Membrane
Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane
There are two main types of membrane receptors
G protein-coupled receptors
Ligand-gated ion channels
© 2014 Pearson Education, Inc. 4

5. Importance of G protein-coupled receptors
Nearly 1,000 different types that we know of.
Involved in:
Embryonic development
Senses of smell
Sense of taste
Maintaining homeostasis!
Ex. Cholera, whooping cough, and botulism are caused by toxins that interfere with G protein-coupled receptors.
Nearly 60% of all medicines influence G protein-coupled receptors.

6. Video: https://www.youtube.com/watch?v=V_0EcUr_txk

7. Signal (ligand)
Receptor
G protein in “off” conformation
1. The G protein is “off” because it is bound to GDP. (GDP is similar to ADP)

8. 2. The ligand binds to the receptor.
Signal (ligand)
Receptor
G protein in “off” conformation
2. The ligand binds to the receptor.

9. Signal (ligand)
Receptor
G protein in “off” conformation
3. The ligand binding to the receptor cause the receptor to change shape.

10. Signal (ligand)
Receptor
G protein in “off” conformation
4. The receptor changing shape is a switch that activates its G protein. The G protein releases the GDP molecule that kept it in an inactive state and binds to GTP instead.

11. 5. When GTP is attached, the G protein splits into two parts.
Signal (ligand)
Receptor
G protein in “off” conformation
5. When GTP is attached, the G protein splits into two parts.

12. Signal (ligand) Receptor G protein in “off” conformation Activated
Cellular response
Activated
enzyme
6. One part of the “split” G protein activates a nearby enzyme that is embedded in the plasma membrane. The activated enzyme catalyzes the production of second messengers. The second messengers are small signaling molecules that diffuse rapidly to spread the signal throughout the cell and elicit a cellular response.

13. Inactive enzyme Activated Signaling molecule GPCR Plasma membrane
Figure 1
Inactive
enzyme
Activated
GPCR
Signaling molecule
Plasma membrane
Activated
G protein
CYTOPLASM 2
Activated
enzyme
G protein-coupled receptors (GPCRs) are plasma membrane receptors that work with the help of a G protein.
G proteins bind to the energy-rich molecule GTP.
The G protein acts as an on-off switch: If GTP is bound to the G protein, the G protein is inactive.
Many G proteins are very similar in structure
Cellular response
© 2014 Pearson Education, Inc. 13

14. To make sure that you understand who G proteins and second messengers work, imagine the following movie scene: A spy arrives at a castle gate. The guard receives a note from the spy, but he cannot read the coded message. Instead, the guard turns to the queen. She reads the note and summons the commander of the guard, who sends soldiers throughout the castle to warn everyone of approaching danger.
You should be able to identify which characters in the scene correspond to the second messenger, G protein, ligand, receptor, and enzyme activated by the G protein.