VOC - Pharmacological Receptors

Question 1

What is the primary function of ligand-gated ion channels like the Nicotinic Acetyl Receptor super-family?

Answer 1

Facilitate fast and self-contained ion flux through the membrane in response to agonist binding

Question 2

Describe the quaternary structure of ligand-gated ion channels

Answer 2

They exist as oligomeric receptors, with pentameric functional receptors composed of a mix and match of individual subunits

Question 3

What are some agonists and some inhibitors of Ligand gated ion channels?

Answer 3

Acetylcholine (Nicotinic) and 5-HT (5-HT3) excite allowing Na+ to flow in

Glycine and GABA inhibit by allowing Cl- to flow in

Question 4

What does the extracellular and intracellular domains contain?

Answer 4

Extracellular Domain (beta pleated)

• Ligand binding
• Post-translational modification (glycosylation)
• Cys-loop

Intracellular Domain

• Protein interaction
• Cell signalling
• Receptor trafficking
• Receptor phosphorylation

Question 5

Where is the acetylcholine binding site?

Answer 5

Acetylcholine binding site is at the alpha subunit and on the neighbouring non-alpha subunit

Many amino acids surround the binding site

Question 6

What occurs at the binding site of acetylcholine?

Answer 6

Ring of benzene rings forms and is made up of major binding amino acids

• Cluster of benzene rings form around quaternary structure of Ach and temporarily bind (not permanent modification)

Question 7

What is the M2 ion channel domain and what are some key features?

Answer 7

M2 is a critical component of ion channel formation

Amino acid alignment that is generally conserved in M2 of this receptor family

• Charged residues (-2)
• Hydroxyl residues 2 and 4
• Hydrophobic residues (9 13 16)

Question 8

How does twisting the agonist binding site influence the M2 ion channel in ligand-gated ion channels?

Answer 8

Agonist binds at top of M2 receptor, and causes twisting of upper sequence

• Does no directly lead to a twisting of transmembrane helices

Lever in place and acts on transmembrane helices and tilts it away from the closure of the ion channel

• Increases the size of the ion channel

Question 9

What are the main structural features of the Tyrosine-Kinase linked receptor?

Answer 9

Secondary structure
Single transmembrane spanning or membrane associated domain

Question 10

Describe the Tyrosine-kinase linked receptor mechanism of transduction (4)

Answer 10

1. Activate by extracellular ligand
2. Conformational change drives receptor dimerization
3. Dimerization activates intrinsic tyrosine kinase or recruits non-membrane-associated kinase
4. Creates site for phosphotyrosine or SH2 binding sites

Question 11

What is the starting point for the synthesis of mineralocorticoids, glucocorticoids, and sex steroids, and how do steroid receptors function (3)?

Answer 11

Cholesterol is the starting point

1. Steroid diffuses into the cell and interacts with the inactive receptor bound to HSP-90
2. Upon steroid binding, conformational change results in dissociation of HSP-90
3. Dimerization occurs (active) and acts to bind to DNA and cause modulation of transcription

Question 12

Describe the structure of steroid receptors

Answer 12

5 DOMAIN STRUCTURE

(N-terminus)
1. Gene transcription

2. Zinc finger DNA binding, Dimer formation
3. Hinge (Dimer formation)
4. Steroid Binding site
5. Nuclear Localisation

(C-terminus)