Lecture 12: nACh Receptor Cation-pi binding

Question 1

What are nicotine receptor related disorders?

Answer 1

Nicotine addiction, nocturnal frontal lobe epilepsy, myasthenia gravis, schizophrenia (mutations in alpha 7),

Question 2

How many subunits do nicotinic Ach receptors have?

Answer 2

5

Question 3

What are the subunits in the muscle nAChRs?

Answer 3

2 alpha, 1 beta, and one gamma (embryonic)/epsilon, 1 delta

Question 4

What are the subunits in the neuronal nAChRs?

Answer 4

only alpha or beta. alpha 2-6 need beta subunits, alpha 7-10 can be homopentamers. alpha4, beta 2 is the most common neuronal structure in the brain

Question 5

What are the similarities between nicotine and Ach?

Answer 5

They are both positively charged quaternary ammoniums

Question 6

What is the transmembrane structure of a nAch R?

Answer 6

It has 4 transmembrane domains. The whole receptor has an extracellular binding domain, where the ligand binds halfway down the receptor, the transmembrane domain, and the cytoplasmic domain.

Question 7

Where does the binding of Ach occur?

Answer 7

At the interface between the alpha/epsilon and alpha delta subunits. The muscle receptor only has two binding sites.

Question 8

How many tryptophans are implicated in Ach binding?

Answer 8

4

Question 9

What technique did they use to show cation-pi binding?

Answer 9

Used artificial amino acids that were fluorinated Trps

Question 10

Which tryptophan was shown to have cation-pi binding?

Answer 10

Trp 149 on B loop

Question 11

What is the aromatic box?

Answer 11

It is the binding pocket, which is surrounded by aromatic residues