Receptors Flashcards
What percentage of drugs act on GPCRs?
50%
Generally how do GPCRs work
- Integral membrane proteins interact with some ligands
- conformational change transferred to G-protein and produces signalling cascade
Where are beta 2 adrenergic receptors mostly found?
In smooth muscle
What hormones do beta2 adrenergic receptors respond to?
Adrenaline and noradrenaline
When beta2 adrenergic receptors are activated by an agonist what are they used to treat?
Asthma and premature labour
When beta2 adrenergic receptors are inactivated by an anagonist what are they used to treat?
Hypertension or cardiac arrythmia
Why was it so difficult to get a structure of beta2 adrenergic receptors?
- Low concentration in tissue
- Unstable once purified
- Flexible and dynamic
Why was T4 lysozyme added to beta2 adrenergic receptors?
- Likes to crystallise
- Enhances ability of a protein to crystallise
Where was lysozyme put into beta2 adrenergic receptors?
It replaced the 3rd intracellular loop
What was used to recombinantly express beta2 adrenergic receptors?
Insect cells
Which part of beta2 adrenergic receptors was deleted to aid crystallisation?
48 C-terminal amino acids
What 3 methods were used to help get a structure of beta2 adrenergic receptors?
- Mutation
- Addition of lysozyme
- Addition of antibody
How were beta2-adrenergic receptors purified?
Using antibodies and ligand affinity columns
What were beta2-adrenergic receptors crystallised in the prescence of?
Carazolol
Why is carazolol used to help crystallise beta2 adrenergic receptors?
It is a partial inverse agonist and so forces the protein into an inactive state
