L5 - GPCRs 1 Flashcards
What are Ionotropic receptors?
(ligand-gated ion channels)
What are Metabotropic receptors?
(G-protein coupled receptors)
How many families of receptor proteins are in GPCRs?
25
Describe the structure of GPCRs? (2)
-Made up of 7 transmembrane domains/helices
-Connected by intracellular/extracellular loops
What are classes of GPCR distinguished by?
-Structural features of extracellular domains and ligand binding site
What is an example of a GPCR?
Example – protease-activated receptors (PAR) in platelets
What are G-proteins regulated by?
-Regulated by ability to bind and hydrolyse GTP (on) and GDP (off)
What subunits are GPCRs made up of? (3)
-Made up of alpha, beta and gamma subunits
What is the mechanism of GPCRs?
-In inactive state – GDP bound to alpha subunit
-Ligand binding causes conformational change in receptor that activates G-protein
-GDP released and alpha subunit separates from other subunits and binds GTP so is now active
-Binds to target protein in membrane to elicit a response within the cell
-GDP then displaces GTP and alpha subunit joins back to beta and game subunit
How is G-protein signalling controlled?
how can it be slowed down/sped up?
-G proteins are timer, rate-limiting step is hydrolysis of GTP to GDP
-Can be slowed and sped up by regulator proteins which stimulate activity of GTPase (hydrolyse GTP) in alpha subunit
What distinguishes different G-protein families?
how many families is there?
-Differences in alpha subunit makes them specific to certain receptors which allows specific response to occur
-There are 6 families
Why do we need secondary messenger signals? (2)
-Single ligand binding to single GPCR results in phosphorylation (activation) of millions of proteins (rapid amplification of signals)
-Doesn’t have to be adenylate cyclase (that binds to enzyme)
