Session 6.3 GPCR's and Nuclear/Intracellular Receptors

Question 1

what are the membrane bound receptors that signal through transducing proteins called

Answer 1

seven transmembrane domain receptors as all have the same 7 transmembrane domain structure

Question 2

what are key features of membrane bound receptors that signal through transducing proteins

Answer 2

coupled through GTP-binding regulatory proteins (G proteins) to enzymes or channels. couple through different G proteins to different effectors

eg: adrenaline binding to beta-adrenoceptors activates the enzyme adenylyl cylase, converts ATP-> cAMP via G protein, Gs
eg: acetylcholine binding to M2 muscarinic acetylcholine receptors stimulates potassium channels to open via a different G protein

Question 3

what is the structure of the G protein coupled receptor

Answer 3

7 transmembrane domains that fold around to form a binding domain for agonist = cleft
ligand binds to N terminus in some cases, in most cases in a cleft formed by transmembranes
in intracellular side, are loops with form the G protein coupling domain (changes in conformation)

Question 4

how does g protein coupled receptors work

Answer 4

at rest, receptors coupled to a protein. G alpha subunit is bound to GDP. when adrenaline binds, GTP is replaces GDP, due to changes in conformation in G alpha subunit. this cause G protein subunit dissociation to produce a G alpha GTP and beta gamma complex which can activate an effector. G alpha GTP activates adenylyl cylase which forms cAMP from ATP, which enters cell

Question 5

how can g protein coupled receptors be inhibited

Answer 5

the target enzyme is susceptible to inhibitory receptors which activates a different G protein, Gi, to target enzyme. a balanced integrated response from both inhibitory receptors and stimulatory receptors at the same time

Question 6

what is the structure of intracellular receptors

Answer 6

binding domain for agonist
domain within them called DNA binding domain (zinc fingers)
a receptor is bound to an inhibitory protein complex

Question 7

how do intracellular receptors work

Answer 7

at rest, receptor is prevented from binding to DNA by inhibitory protein complex making it inactive
binding of steroid hormone, receptor undergoes conformational change, dissociates inhibitory protein complex and reveals dna binding site, which can be bound to to affect transcription

Question 8

how are intracellular receptors classified

Answer 8

receptors different depend on amino acid sequence
but form part of intracellular receptor family for hydrophobic signals as still similar as DNA binding domain does not move and similar pattern

Question 9

what are examples of intracellular receptor family

Answer 9

cortisol
oestrogen
progesterone
vit D
thyroid
retinoic acid

Question 10

how is cellular signalling amplified

Answer 10

activated receptors activates G protein which activates a second G protein and a third and a fourth so four effector proteins so lots of cAMP. which activates protein kinase A which phosphorylates target substrate molecules (significant amplification each time), more phosphorylation and activation

Question 11

what can activating a receptor lead to

Answer 11

cellular activation or inhibition depending on receptor activated
eg: pacemaker cells
noradrenaline -> Beta 1 - adrenoreceptors -> increases HR
acetylcholine -> M2 muscarinic receptors -> slows heart rate
eg: hepatocytes - both receptors activated but response is opposing
insulin - glycogen stimulus
glucagon - glycogen break down