G-protein Coupled Receptors Flashcards
3 main types of cell surface signalling receptors
- G-protein-coupled receptors
- Enzyme-coupled receptors
- Ion-channel coupled receptors
Many intracellular signalling proteins act as molecular switches, transitioning from …
… inactive to active upon recieving a signal.
Once activated, molecular switches can…
… stimulate or suppress other proteins in the pathway until switched off by another process.
Proteins that act as molecular switches are usually of of two classes.
- Proteins that are activated or inactivated by phosphorylation.
- GTP-binding proteins.
Phosphorylation-regulated proteins
- undergo activation or inactivation through the addition or removal of phosphate groups.
- Protein kinases attach phosphate groups,
- protein phosphatases remove them.
GTP binding proteins
- These proteins switch between active (GTP-bound) and inactive (GDP-bound) states.
- Upon GTP binding they activate,
- When there is GTPase activity they inactivate.
- Many GTP-binding protein possess intrinsic GTPase activity, leading to self-inactivation.
Two main types of GTP-binding proteins are involved in intracellular signalling
- Trimeric G proteins, which relay signals from G-protein-coupled receptors,
- Monomeric GTPases, which assist other cell-surface receptors.
What are GPCRs
GPCRs are the largest family of cell-surface receptors that play a crucial role in transmitting signals from the external environment to the inside of cells.
Typical structure of GCPRs
Feature 7 hydrophobic domains aross the lipid bilayer
Trimeric G-proteins
- There are several varieties of specific trimeric G proteins.
- All of them have a similar general structure and operate in a similar way.
- They are composed of three protein subunits—α, β, and γ—two of which are tethered to the plasma membrane by short lipid tails.
- In the resting state it is tethered to the inner leaflet of the plasma membrane and the α subunit is associated with a molecule of GDP.
When an extracellular signal molecule binds to a GPCR, the receptor protein undergoes a conformational change that enables it to activate a…
… a trimeric G protein located on the cytosolic side of the plasma membrane.
Process of activation of G-protein
- Signal molecule binds to receptor
- α subunit decreases its affinity for GDP and exchanges it for GTP.
- The subunits break into an activated α subunit and an activated βγ complex.
- The two activated parts directly interact with target proteins within the plasma membrane.
- The activation of the proteins may relay the signal
The length of time the subunits are “turned on” is determined by the …
…α subunit, because it can hydrolyse GTP to GDP and return the whole G-protein to its original conformation.
Ion channels as target proteins
- directly regulate the activity of ion channels causing an immediate change.
- For example when the GPCR activates the trimeric G protein, the βγ complex binds to the intracellular face of a K+ channel in the plasma membrane of the pacemaker cell, forcing the ion channel into an open conformation
- This channel opening slows the heart rate by increasing the plasma membrane’s permeability to K+, which makes it more difficult to electrically activate.
- The original signal is terminated—and the K+ channel recloses—when the α subunit inactivates itself by hydrolysing its bound GTP, returning the G protein to its inactive state
Heartbeat in animals is controlled by two sets of nerves:
- one speeds the heart up, the other slows it down.
- The nerves that signal a slowdown in heartbeat do so by releasing acetylcholine, which binds to a GPCR on the surface of the heart pacemaker cells.
