receptor structure and signal transduction

Question 1

name an example of a pentameric, tetrameric and trimeric ligand gated ion channel

Answer 1

pentameric: nAChRs
tetrameric: glutamate receptors e.g NMDA
trimeric: ATP (P2X) receptors

Question 2

how many transmembrane alpha helices do ligand gated ion channels have

Answer 2

pentameric: 4
tetrameric: 3
trimeric: 2

Question 3

where are the N and C terminus located for LGICs

Answer 3

pentameric: both N and C are extracellular
tetrameric: N terminus extracellularly C intracellular
trimeric: both intracellular

Question 4

what are cys loop receptors

Answer 4

pentameric ligand gated ion channels

Question 5

what time scale to LGICs act over

Answer 5

milliseconds

Question 6

what 2 main enzymes do GPCRs activate/ inhibit and what second messengers do they produce?

Answer 6

adenylate cyclase: cAMP

phospholipase C: IP3

Question 7

how many subunits do GPCRs have and how many transmembrane alpha helices?

Answer 7

just 1 subunit/ monomeric

7 transmembrane alpha helices domains

Question 8

what are G proteins?

Answer 8

heteromeric complexes (alpha beta gamma subunits) which catalyse interconversion of GTP and GDP

Question 9

what time scale do GPCRs act over

Answer 9

seconds

Question 10

give three types of examples of signalling molecules that use kinase linked receptors

Answer 10

peptide hormones, growth factors and cytokines

Question 11

what domains are there in kinase linked receptors and where are the N and C terminus

Answer 11

extracellular ligand binding domain containing N terminus,
single transmembrane domain,
intracellular catalytic effector domain which contains C terminus

Question 12

give examples of kinase linked receptors

Answer 12

tyrosine kinase receptors and tyrosine kinase linked receptors, insulin receptor

Question 13

what is the time scale of kinase linked receptors?

Answer 13

hours

Question 14

what do nuclear receptors do and how do they differ from other receptors?

Answer 14

regulate gene transcription, receptors are soluble

Question 15

how many regions do intracellular receptors have?

Answer 15

2; DNA binding domain and a ligand binding domain

Question 16

what happens to intracellular receptors after the ligand binds

Answer 16

the receptors form dimers, the dimeric ligand bound receptor acts as a transcription factor

Question 17

what is the time scale for intracellular receptors?

Answer 17

hours/ days

Question 18

how is the therapeutic index calculated?

Answer 18

LD50/ ED50

Question 19

how many isoforms are there of nAChR subunits?

Answer 19

10 isoforms of alpha
4 isoforms of beta
1 gamma 1 delta 1 epsilon

Question 20

what happens after a GPCR is activated

Answer 20

ligand binding to receptor causes conformational change which causes G protein to interact with the 3rd intracellular loop

binding of alpha subunit to activated receptor causes GDP to be exchanged for GTP

this causes G protein to be activated and the beta gamma complex dissociates and anchors itself to plasma membrane

GTP bound alpha subunit binds with effector such as adenylate cyclase or phospholipase C

The hydrolysis of GTP causes the alpha subunit to dissociate from effector

Question 21

what are GAPs

Answer 21

GTPase- activating proteins, regulators of G proteins that speed up hydrolysis of GTP so effects are shortened

Question 22

what are the different types of G protein

Answer 22

Gs: activates adenylate cyclase and activates calcium channels

Gi: inhibits adenylate cyclase and activates potassium channels

Gq: stimulates phospholipase C, activates potassium channels

Go: stimulates phospholipase C, activates potassium channels, inactivates calcium channels

Question 23

give examples of the different types of GPCR

Answer 23

Gs: beta adrenoceptor
Gi: alpha 2 adrenoceptor
Gq: alpha 1 adrenoceptor
Go: M2 muscarinic

Question 24

what happens when agonists bind to kinase linked receptors?

Answer 24

receptor dimerisation

conformational change means active sites are now available to bind ATP which causes autophosphorylation of tyrosine residues

phosphorylated tyrosine residues act as docking sites for effector molecules with src homology domains such as SH2 and SH3 domains, many different effectors may interact with same receptor

Question 25

where are intracellular receptors located

Answer 25

cytoplasm or nucleus

Question 26

what are the responses after intracellular receptors are activated

Answer 26

early primary response is synthesis of a few different proteins in primary response, one of these proteins shuts of primary response genes and one of these turns on secondary response genes which produce secondary response proteins