G Proteins Flashcards
The G protein coupled receptor is the largest of the receptor families.
Describe its transmembrane domains? How many are there? How are they arranged? Whats special about alpha helix 3
They have 7 transmembrane domains which anchor into the plasma membraneS
These transmembrane domains aren’t arranged in rows, they are folded around each other
These transmembrane domains are alpha helices
Alpha helix 3 is always orientated towards structures in the cell walls. So it points towards the middle of the cell.
What does alpha helix 3 of g proteins do? What are typical of all of the transmembrane domains? And what Is important about the 5th and 6th transmembrane domains?
alpha helix 3 is responsible for transduction outside of the cell, and transferring info into the cell
These domains are made of loops that are on the intracellular side of the cell
The 5th and 6th transmembrane domains tend to be longer than the other domains
Configurations of the transmembrane domains of G proteins? What in particular is special about the C and N terminus?
Their amino ‘’n’’ terminus points out of the cell
The c terminus points in
There is a difference in length of these terminals in different receptors
The n terminus contributes to ligand binding
The C terminus regulates receptor function.
What are conserved features of all membrane receptors? Where is most diversity in different G proteins?
They all have signal transducing domains - these are parts of the receptors which cause changes in the cell
Most diversity of receptors is seen in the parts of the receptors which are responsible for detecting stimuli
How are g proteins formed from there 7 transmembrane domains? And what state do these transmembrane domains oscillate between?
They are all folded up to create the g protein.
These transmembrane domains oscillate between a resting and active state
What is a typical feature when G proteins isn’t active? What happens to transmembrane proteins 5 and 6 When the cell is active?
Transmembrane proteins 5 and 6 are close together.
The cytoplasic side of the receptor (so the side in the cell) is pinched and closed
Transmembrane 5 and 6 move slightly when active. This opens the cytoplasmic cleft.
What do agonists do when they bind to g proteins?
They bind to transmembrane 3 on g proteins
This binding causes the stabile conformation of the transmembrane proteins of the g protein allowing the protein to signal.
The binding also releases energy which goes to transmembrane 5 and 6. This causes them to undergo critical movements which the agonist stabilises.
Key note about how far GPCRS stick out of the membrane?
They dont stick out very much
In what orientation must a ligand enter a cell?
In the correct orientation.
In terms of agonist bind how are GPCRS different?
What is the mechanism and structure for the detection of glutamate on G proteins
Each agonist has different mechanisms of binding
Glutamate binds to these G proteins in a similar way to how they bind to ligand gated channels
Alike the ligand gated channels:
These receptors have very large extracellular domains made by a very long amino terminus
These also have a clam shell shape which ligands binds to.
How is the glutamate receptor on GPCR different to normal GPCR?
These glutamate receptors g proteins rely on a clam shell trapping molecules
Whereas normally ligand molecules usually enter the GPCRs at the 3 transmembrane domain
What is the biggest sub family of the GPCRS?
The prototypical adrenoreceptors.
These detect small molecules like dopamine and ACh
THUS most small neuropeptide transmitters often work through GPCRS
What are odourant receptors?
These are GPCR receptor proteins.
There are over 700 different receptors for different odours
These odours are volatile
Different olfactory sensory neurones remember expresses different repertoires for different odours.
What do PAR receptors detect? What are they important for?
They detect thrombin
They are important for blood clotting and wound healing.
Thrombin is a protease remember
How does the thrombin protein affect PAR receptors?
When it comes along and encounters receptors
It cleaves amino terminus at specific of the receptor
Then the peptide leaves
The remaining part of the amino terminus folds down and goes into the ligand binding site. This activates the receptor.
How does a blood clot work? And how do GPCRs get involved?
This is initiated when there in break in the endothelium lining of blood vessels
This attracts red blood cells and other factors to the area where there is a breach.
Blood escapes to try and plug the hole
GPCRs are important in the blood clotting. The thrombin receptor has to be activated (to activate the protein).
And also the ADP receptor is also needed - this is the purinergic receptor.
The GPCR recognises extracellular ATP and ADP
GPCRs are stimulated by thrombin, how do GPCRs stop blood clots? And how can drugs which stimulate these reduce risk of thrombosis?
They work at the level of platelets by stopping them from sticking together. Stopping blood clots.
Drugs which interact with these GPCRS can thin blood, reducing thrombosis risk.
Before a G protein is bound to a receptor. What state is the receptor in? What happens when the receptor becomes active? What is bound to the Alpha helix at this stage? And what is this exchanged with
Before a G protein complex is bound to its receptor. The receptor is in the membrane as the inactive form.
When it becomes active. This is when it is bound to an alpha and a beta gamma subunit.
At this stage the alpha helix has a GDP bound. This is exchanged for a GTP by GTPase whilst the G protein is associated with the receptor
What is a heterotrimeric and a monomeric G protein?
The heterotrimeric G protein is when the alpha sub unit of the G protein is bound to the beta and gamma sub units. Think of this when the G protein is bound to the receptor
The monomeric G protein is when the alpha sub unit of a G protein is dissociated from the beta gamma sub units. Think of this as when the G protein is away from the receptor.
What happens when the GDP is exchanged for GTP on the alpha subunit of the G protein. This is when its bound to the receptor
The alpha and beta gamma sub units can now dissociate from the receptor and go onto work on downstream effectors.
Whats the similarities between the heterotrimeric G protein and the monomeric G protein
In ref to the alpha sub unit
The monomeric G protein (When the G protein Alpha sub unit is alone) has a GTP exchanged for a GDP by a GTPase
This is thanks to GEF - guanine exchange factors
The heterotrimeric G protein (when the G protein alpha sub unit is bound to the beta gamma sub units at the receptor) it has a GDP (note what this says) to a GTP
This is also thanks to GEFs. In this case the receptor acts as the GEF
What controls the timing of the exchange of GTP for GDP in monoeric G protein alpha sub units?
This is controlled by GAPs
These are extrinsic proteins.
This likely occurs when the monomeric g proteins are bound to effectors like adenyl cyclase.
So what does the heterotrimeric G protein have bound after GTPase has done its jobs?
And how about the monomeric G protein
After the GTPase done its job
The heterotrimeric G protein (when the alpha sub unit is bound to the beta gamma sub units and the receptor) the G protein has a GTP bound
The monomeric G protein has a GDP bound
(The GTP which was orignally bound is swapped for a GDP by the GTPase. This is when the monomeric G protein is bound to an effector like adenyl cyclase).
There are also proteins which control the rate of GTPases action on the alpha sub unit of heterotrimeric G proteins (the alpha subunit bound to the receptor)
What are these proteins? And the ones that increase the rate of the GTPase’s, what do they turn off quickly? What does phospholipase C do?
These of RGS proteins
They either speed up or slow down the rate of GTPase action.
The ones which increase GTPase action turn off signalling quicker
Phospholipase C (an effector) can also work as a RGS to speed up GTPase action on the alpha sub unit of the heterotrimeric G protein
