Session 6.2: Ligand Gated Ion Channels and Kinases

Question 1

what are the 4 types of signal tranduction in order of speed

Answer 1

1. membrane bound receptors with integral ion channels - rapid flux of ions which changes membrane potential
2. membrane bound receptors with integral enzyme activity - conformational change is communicated directly within the protein
3. membrane bound receptors which couple to effectors through transducing proteins - transducing protein might have to move to effector to activate
4. intracellular receptors -receptors are transcriptional factors so need transcription and translation for response

Question 2

what is the structure of the nicotinic acetylcholine receptor

Answer 2

a family of ligand gated ion channels
pentameric complex - 5 similar subunits = receptor. alpha subunit bind the acetylcholine receptor
pore down centre of molecule - selectivity of cations due to rings of negative charged amino acids placed around mouths of channel
gate is opened by binding of acetylcholine, causes conformation channels, opens to allow travel of sodium and potassium - changes membrane potential

Question 3

what are examples of membrane bound receptors with integral ion channels with their ion selectivity (classic pentameric format)

Answer 3

• nicotinic acetylcholine receptor -> gated sodium, potassium and calcium channel = depolarisation
• GABA -> gated chloride channel = hyperpolarising which is inhibitory
• glycine -> gated chloride channel = hyperpolarising which is inhibitory
• glutamate -> gated entry of cations = depolarising

Question 4

what are examples of membrane bound receptors with integral ion channels with their ion selectivity (non classical)

Answer 4

• IP3 -> gated release of calcium from ER = different structure
  others are also available such as atp sensitive potassium channel

Question 5

what is the structure of membrane bound receptors with integral enzyme activity

Answer 5

membrane spanning domain = alpha helix, so conformation change in binding domain causes conformaion change in catalytic domain. subunits can move against each other revealing catalytic domain to activate them

Question 6

what are examples of membrane bound receptors with integral enzyme activity

Answer 6

Atrial Natriuretic Peptide receptor - linked directly to enzyme, guanylyl cylase which causes GTP -> CGMP (secondary messenger)
Growth Factor receptors (insulin, epidermic GF, platelet derived GF) - linked directly to enzyme, tyrosine kinase on inside of membrane, which takes ATP and transfer a phosphate onto a protein kinase - phosphorylates protein

Question 7

how does signalling via tyrosine kinase linked receptors work

Answer 7

when agonist binds to receptor, receptor phosphorylates itself on opposite strand (autophosphorylation). the tyrosine phosphate recognise by binding sites, bring enzyme to receptor so enzyme is phosphorylated so send off activated enzyme into cell. between enzyme and receptor could be a transducer which contain tyrosine phosphorylation sites so transducer protein phosphorylated by receptor, which then acts as a docking site for enzymes to bring to receptors to activate by phosphorylation

Question 8

what are the binding sites called on tyrosine kinase linked receptors

Answer 8

src homology domain 2 (SH2)

Question 9

what are possible examples of domain transducer found on tyrosine kinase linked receptors

Answer 9

insulin receptor substrate 1 (IRS-1) , Grb2

Question 10

how is the structure of the insulin receptor different to other tyrosine kinase linked receptors

Answer 10

tetrameric receptor of two alpha subunits and two beta. Synthesised as one chain. disulphide links are formed between alpha and beta subunits post translationally

Question 11

what is an example of tyrosine kinase linked receptor

Answer 11

insulin