L9 - G-protein coupled receptors

Question 1

structure of GCPRs

Answer 1

7 tarsnmebrane alpha helices that span cell membrane

extracellular N-terminus that binbds to ligand

intracellular C-terminus that interacts wuth intracelluakr signalling proteins –> G-proteins

Question 2

why is the 7 tranbsmembrane alpha helices crucial to the GPCRs function

Answer 2

ligand binding causes comformational change in receptor

= change is transmitted through the transmembrane domainbs into intracellular side –> GCPR can then activate G-protein

different GCPRs recognise different ligands BUT the mechansim is the same

Question 3

describe coupling of GCPRs to heteromeric G-proteins (⍺,β,γ)

Answer 3

1. inactive state the G-protein is bound to GDP
2. liagnd binding -> active GPCR acts as GEF

= exchange GDP for GTP on G⍺ subunit

3. G⍺ subunit disociates from Gβγ dimer

= both the a AND the By have effector affects

Question 4

describe the signal amplification of GCPRs

Answer 4

1 GCPR can activate many G-proteins

1 G⍺ subunit can activate 1 enzyme -> can actuvate thousands of secondary messanfger molecules

= adenyl cyclase -> cAMP

each secondary messanger can activate multiple downstream targets -> cascade of intracellular events

= small amount of ligand causes a large response

Question 5

name 2 reguatory mchanims that prevent overstimulation of GCPRs due to their high affinity for ligands

Answer 5

GRKs - receptor phosphorylation

arrestin - binds to recepot blcoking further G-protein activation