Receptor Diversity Flashcards
(53 cards)
The term ‘receptor’ most usually describes a specialised protein which specifically recognises and responds to a single endogenous molecule (or very small group of closely related molecules). Give an example.
Adrenoceptors recognise adrenaline and noradrenaline, but do not recognise closely related molecules such as tyrosine, DOPA, dopamine etc.
A receptor only response to one/ very limited number of endogenous ligands. However, it is possible to synthesise chemicals which can also interact with the receptor. How may this occur in nature?
One biological organism generates a chemical that can be administered (e.g. through bite/sting) to another species and, via receptor interactions, cause a change in the targeted animal’s physiology (e.g. incapacitation/ paralysis)
How does snake venom incapacitate people who are bitten with it?
Contains Ca2+/K+ channel blockers
How can biologically- or chemically- generated ligands act at a receptor?
- mimic the action of the endogenous ligand (AGONIST)
- block the action of the endogenous ligand (ANTAGONIST)
- act at a site distinct from the lignd binding (ORTHOSTERIC) site - ALLOSTERIC MODULATOR
How does venom from the green mamba act to incapacitate its victim?
Muscarinic receptor antagonist - acts as a negative allosteric modultor
Give an example of:
- a ligand-gated ion channel
- a kinase-linked receptor
- a GPCR
- a nuclear receptor
- nicotinic ACh receptor
- EGF receptor
- mACh receptor
- steroid hormone receptor
With the exception of the insulin receptor, what structure do RTKs take?
Single, TM-spanning polypeptides which DIMERIZE on ligand-binding
Following dimerisation, what happens to RTKs?
The C-term domains of each monomer phosphorylates the other monomer (AUTOPHOSPHORYLATION) on specific tyrosine residues to form phosphotyrosine (Y-P) docking sites for proteins possessing SH2 domains. This allows RTK to act as a scaffold for intracellular signalling pathways to be assembled and initiated
What residues in RTKs serve as docking sites for proteins possessing SH2 domains?
phosphotyrosines
Phosphotyrosines on RTKs serve as docking sites for proteins containing which domains?
SH2 domains
What does the presence of phosphotyrosines on RTKs allow for?
Docking of proteins containing SH2 domains, which allows the RTK to act as a scaffold for intracellular signalling pathways to be assembled and initiated
How does the insulin receptor differ from most RTKs?
It is made up of 4 subunits and comes in a pre-dimerised form
The insulin receptor is ATYPICAL. Give an example of an RTK that is more typical. How is it activated?
PDGF receptor. Ligand binds, 2 monomers dimerise, intracellular domains with tyrosine kinase activity are activated and phosphorylate tyrosine residues. Phosphotyrosines act as docking sites for proteins containing SH2 domains.
What percentage of identified genes in the human genome are GPCRs?
1-2%
What 4 structural features do all GPCRs share?
- Single polypeptide chain (300-1200 amino acids in length)
- Extracellular N-terminal
- Intracellular C-terminal
- 7TM-spanning domains
Give some examples of drugs targeted against GPCRs
Zyprexa - 5-HT(2A) serotonin receptors - schizophrenia/psychosis
Plavix - P2Y(12) (ADP chemoreceptor) - thrombosis
Fluticasone/Salmeterol - B2-AR - asthama
Which family of GPCRs do adenosine, ATP, opiates, odorants, retinal, catecholamines etc bind do?
Family 1A
What family of GPCRs do peptides, cytokines, thrombins etc bind to?
Family 1b
What family of GPCRs do glycoproteins and hormones (LH, TSH, FSH) bind to?
Family 1c
Which family of GPCRs do calcitonin and secretine bind to?
Family 2
What family of GPCRs do glutamate, calcium, GABA(B) and pheromones bind to?
Family 3
Which is the largest family of GPCRs?
Family A (1) (rhodopsin-like)
Where does the ligand bind to the receptor in Family A GPCRs?
Specific amino acids within the TM regions contribute to the ligand binding site
What are RAMPs?
Receptor activity-modifying proteins
