Lecture 4 Flashcards
What is an ionotropic receptor?
A receptor linked to ion channels
What is a metabotropic receptor?
A G-protein coupled receptor
What is a catalytic receptor?
A receptor linked to kinases
What is a nuclear/intracellular receptor?
A receptor linked to gene transcription
What is the general structure of an ionotropic receptor?
4-5 transmembrane domains, with one binding domain
What is the general structure of a G-protein coupled receptor?
7 Transmembrane domains, often 2 binding sites which can either cytoplasmic or within the membrane, and a G-protein coupling domain which transmits the signal to the G-protein and the structure of which protein is recruited
What is the general structure of kinase linked receptors?
1 transmembrane domain, one binding domain and one catalytic domain
What is the general structure of a nuclear receptor?
one binding domain and a DNA binding domain, NO transmembrane domain
What are examples of ionotropic receptors?
nicotenic acetylcholine receptors (nACh) and GABAa
How fast are ionotropic receptors?
Very fast act within ms as the signal is very simple
What is the mechanism of ionotropic receptors?
Binding of the agonist causes a conformational change in the receptor which leads to ion channel opening
What effects can different agonists have on ionotropic receptors?
Some such as nAChR can cause increased channel opening time, while others such as glutamate can cause an increase in channel conductance
Others can alter the charges lining the pore to alter the selectivity of the ion channel
What is the structure of the nACh receptor?
Pentamer of two alpha units, one gamma unit, one beta and one sigma unit, with two ACh binding sites between the alpha and gamma subunits
What drugs affect the GABAa receptor?
GABA opens the pore to allow Cl- flow inhibiting neuronal firing, benzodiazepines and barbiturates facilitate the opening of the channel by increasing either the rate r duration of channel opening
How fast are G-Protein linked receptors?
fast actions occur within seconds
What are examples of G Protein linked receptors?
mAchR, adrenoreceptors
What is the mechanism of G-protein linked receptors?
Binding of the agonist binds to the G protein causing a conformational change, this results in the G protein having GDP replaced by GTP which allows signalling to target proteins to cause the desired biological effect, the GTP will eventually be hydrolysed leading to the end of the signal
What are the G protein families?
Gs (stimulatory), Gi (inhibitory), Gq
What is an example of a target protein of a G-protein linked receptor and what is its function?
Adenylate kinase can be activated, this can generate cAMP as a secondary messenger which will activate various protein kinases
If Gi is activated then there will be a decrease in cAMP if Gs is activated there will be an increase in cAMP
What is the role of protein kinases?
Enzymes that attach phosphate groups to proteins (like PKA, PKC) leading to changes in structure and function, this can sometimes operate on 3rd messengers to cause regulations of genes
What is bi-directional control with regards to G-proteins?
Different G-receptor complexes allow opposing effects on an enzyme allowing for a graded signal and a maintenance of balance
What is the function of Gq?
Gq activates phospholipase C which activates IP3 which can open Ca2+ channels on the ER or SR, this can activate protein kinase C which will result in the phosphorylation of substrates
this pathway is key to smooth muscle contractions
How fast are catalytic receptors?
Can act between minutes or days, dependent on the pathways involved
What are examples of catalytic receptors?
Tyrosine kinase and guanylate cyclase receptors which respond to ligands such as growth factors, hormones and cytokines to trigger a kinase cascade
What is the Ras/Raf/MAP Kinase pathway?
A pathway involved in cell differentiation,
Growth factor binds onto a receptor causing dimerisation and autophosphorylation of tyrosine residues on the intracellular tyrosine kinase domains, this results in the binding of an SH-2 domain protein which becomes phosphorylated and signals Ras to become activated, this activates Raf, which results in a phosphorylation chain moving from Raf to Mek to Map kinase which phosphorylates various transcription factors altering gene transcription
What is the Jak/Stat pathway?
Cytokine binds to a receptor which is a dimer, when both of the dimers are bound a conformational change is induced resulting in Jak being recruited and phosphorylating tyrosine residues Stat then binds and becomes phosphorylated leading to it to dimerise and alter gene transcription
How fast are intracellular receptors?
Slow acting often taking hours or days to take effect but have a long lasting effect
What are examples of of intracellular receptors?
Steroid hormone receptors
What is important about the ligands of intracellular receptors?
need to be able to easily penetrate the cell membrane and therefore are frequently lipid soluble
What is the mechanism of intracellular receptors?
Typically there is an inhibitor bound to the ligand binding domain this will be removed by the hormone which will allow the receptors DNA binding domain to bind to highly conserved regions of DNA to alter gene transcription and protein synthesis
