receptor mec 2

Question 1

how many proteins in a gpcr

Answer 1

he receptor is made out of 1 protein instead of 5 and it coils up to form a 3d structure.

Question 2

describe the effect of gpcr

Answer 2

It causes the interaction with G proteins. These g proteins then interact with key enzymes so there is a slower effect, however a more sustained effect. This is because even if the aognist is unbound from the receptor, the enzyme may still be activated

- So slower response than ligand gated ion channels but may be longer lasting. 
- They are faster than tyrosine kinase linked receptors and ncueleur receptors.

Question 3

describe the structure of gpc

Answer 3

· The transmembrane domains (blue rectangles) are clumps of amino acids that prefer to be in the lipid phase in the membrane.
· The agonist binding site is the amino terminus that sticks out in the external solution. The large intracellular C-terminus interacts with the alpha subunit of G-proteins which binds to GTP or GDP (GTP/GDP binding proteins aka G-proteins). The large a-subunit is anchored in the membrane by the smaller B/Y- subunits.
· In the absence of the chemical, the a-subunit binds to GDP which allows it to ‘hold hands’ with the Y-subunit.

Question 4

how many transmembrane domains do gpcrS have

Answer 4

All G protein coupled receptors have 7 transmembrane domains - also known as heptahelical - 7 helices

Question 5

describe the g protein couple super family

Answer 5

• The protein coils up and a ligand binding domain is present.
  
  • It can incorporate around 800 different receptors.
  • The different types of ligands that activate the receptors examples : amino acids such as gluatamate, biogenic amines such as noradrelaline, there are also receptors activated by calcium ions , nucleosides, nucleotides, lipids, peptides such as cholecystokinin. Some receptors activated by the action of proteases that remove a part of the amino terminus causing its activation.
  • There is a long C terminus that allows the receptor proteins to interact with the proteins that give them their name
    In G proteins, the G stands for GTP/GDP.

Question 6

where does the receptor interact with the alpha subunit

Answer 6

at the c terminus

Question 7

what happens when u activate the gpcr

Answer 7

Initially when the receptor isn’t activated, the large alpha-subunit is bound to GDP which gives it a conformation that allows it to interact with the beta and gamma subunits that anchor it in the membrane. So in the absence of receptor activation, the alpha subunit has a high affinity for GDP and the beta and gamma subunits
An exchange occurs at rest in the absence of receptor activation.
The alpha subunit binds the GDP and can then quickly exchange it for GTP when the agonist binds to the receptor. ALPHA SUBUNIT- c terminus.
The activated alpha subunit, when binding GTP , has a lower affinity for beta and gamma, and a higher affinity for a different enzyme
Therefore the alpha subunit is broken down into main 4 subunits: alphaS, alphai, alphaq and alpha12. These then go off to alter enzymes. When the agonist dissociates from the receptor, the alpha subunit affinity changes and goes back to being associated with beta and gamma subunits.

Question 8

what do these g proteins do

Answer 8

• When the receptor Is activated, it interacts with an enzyme. The enzyme produces products which create the cellular response.
  
  • The response is cyclical, so it doesn’t persistently activate the enzyme, it returrns to the receptor complex, leading to cyclic activation.
    So the alpha subunit is an intermediatory, from the receptor to interact with an enzyme

Question 9

outline the steps in the g protein cycle.

Answer 9

• G protein cycle
  
  1. There is the 3G proteins
  2. A free activated alpha subunit whith a GTP bound forms as a consequence of an activation of the G protein coupled receptor. This causes it to have a lower affinity for the beta and gamma subunits so it dissociates from them.
  3. It interacts with the target enzyme and modifies it. But the alpha subunit has an inherent GTPase ( removes phosphate groups). As a consequence of the GTPase, the GTP is hydrolyed to a GDP.
  4. In this energetic state, the alpha subunit has a higher affinity for the beta gamma subunits than it does for the enzymes.
  5. So it dissocites from the enzyme and reassociates with the beta and gamma subunits.
     When the receptor is stimulated, there is the activation of the alpha subunit, exchange of GDP to GTP and the dissociation of the othersubunits again and activation of the enzyme again.

Question 10

how is adenylate cyclase altered ?

Answer 10

• the agonist binds to the gpcr and this causes the alpha subunit to exchange its GDP for GTP, this causes the alpha subunit to have a lower affinity for the gamma and beta subunits so it dissociates from them.
• the alpha subunits then interact with the adenylate cyclase enzyme.Two alpha subunits interact with adenylate cyclase: G alpha S stimulates adenylyl cyclase , whereas Galphai inhibits adenyly cyclase
  1. Adenylase cyclase creates cAMP from ATP.
  2. cAMP can function independelty but achieves a lot of work by converting inactive protein kinase A to activated PKA.
  3. Pka phosphorylates proteins where any protein that can be phosphrylated will be phosphrylated by pka.
  4. cAMP levels are decreased as it is broken down by phsophodiesterase - PDE. These are potential targets to modify post receptor signalling. Phosphoiesterase inhibitors keep cAMP levels high e.g Coffee molecules contain phosphodiesterase inhibitors so cAMP levels remain high which give extra forceful contractions of the heart.

Question 11

what does g alpha q/11 do

Answer 11

What does the alpha Gq/11 subunit do ?
It works on the activated enzyme phospholipase C. the main isoform is beta.
Phospholipase C works on a phospholipid found in the cell membrane - PIP2 - minor constitutent forms around 10% of the membrane lipids.
Phospholipase C cleaves Pip2 to produce IP3, a water soluble liagand and Diacylglycerol - DAG which stays in the lipid phase.
IP3 can interact with its own receptor located on many intracellular organelles, in the main endoplasmic calcium stores which leads to a release in calcium.
So if there is a cellular response involved the ceullar rising in calcium, such as secretion of enzymes or contractile mechanisms, the receptors involved are linked to phospholipase C.
Deg can function independently and can also activate a different protein kinase - protein kinase C which is also calcium dependent.

Question 12

what is the target enzyme, substrate second messenger, kinase and effector of of Galphas.

Answer 12

adenylate cyclase – atp – camo– ion channels+ protein kinase a- phosphorylates

Question 13

what is the target enzyme, substrate second messenger, kinase and effector of galphai

Answer 13

adenylate cyclase – atp – camp

Question 14

what is the target enzyme, substrate second messenger, kinase and effector of gaq/11

Answer 14

phospholipase c, pip2—ip3(contractileproteins) + dag – ion channels+proteinkinasec

Question 15

gpcr may be slower than ligand gated ion channel receptors but

Answer 15

• G protien coupled receptors may be slower than ligand gated receptors however are very efficent at amplifying signals.

Question 16

give an example of how gpcrs amplify signals

Answer 16

1 adrenaline molecule + 1 b-AR = 10,000 cAMP molecules
These cAMP molecules can then activate protein kinase A which can then phosphorylate a number of targets, and depending on what that cell is, protein kinase A will have its effect

Question 17

receptors are subdivided into superfamilies based upon

Answer 17

superstructure

Question 18

why do gpcrs produce slower responses ?

Answer 18

because the receptor is coupled to an enzyme via an intermediate protein