Signal Transduction Flashcards
Describe the structure of GPCRs
Single polypeptide chain
7-transmembrane domains
Extracellular N-terminal, intracellular C-terminal
What are the 3 superfamilies of receptors?
Ligand gated ion channels
Receptors with intrinsic enzyme activity
G-protein coupled receptors (GPCRs)
Where on GPCRs can ligands bind?
To the N-terminal region (eg peptides, glutamate)
To the 3rd cytoplasmic loop- between the 2nd and 3rd transmembrane domains (eg ACh, adrenaline)
Give an example of a Beta adrenoceptor agonist and its use
Salbutamol, anti-asthmatic
Give an example of a u-opioid receptor agonist and its use
Morphine, anaesthesia
Give an example of a beta adrenoceptor antagonist and its use
Propranolol/atenolol, hypertensive drugs
Give an example of a D2 dopamine receptor antagonist and its use
Haloperidol, anti-schizophrenic
Give some examples of mutations to GPCRs
Loss of function mutation to rhodopsin causes Retinitis Pigmentosa.
Loss of function mutation to V2 vasopressin receptor causes Nephrogenic Diabetes Incipidus
Gain of function mutation to LH receptor causes Familial Male Precocious Puberty
What stimuli can GPCRs respond to?
Sensory GPCRs sense light, odours, taste
Other GPCRs sense to changes in extracellular ions, neurotransmitters, hormones, large glycoproteins
How do GPCRs change cellular activity?
Agonist binding results in a conformational change, which allows interaction with a Guanine-nucleotide Binding Protein, a G-protein.
Describe the structure of a G-protein
They are heterotrimeric, with alpha, beta and gamma subunits.
GDP is bound to the alpha subunit
Describe the events that follow GPCR G-protein interaction
This activates the G-protein.
The GDP on that alpha subunit is exchanged for GTP by Guanine Nucleotide Exchange Factors (GEF).
The complex dissociates into alpha-GTP and free beta-gamma subunits which interact with effector proteins
How is the signal terminated?
Interaction with effector proteins lasts until the alpha subunit GTPase activity hydrolyses the GTP to GDP.
The alpha-GDP and beta-gamma subunits reform a heterotrimeric complex which is inactive.
How can magnitude of the signal be regulated?
By regulation of the GTPase activity by GTPase Activating Protein (GAP).
This alters the time that the subunits interact with effector proteins before reforming the heterotrimeric complex.
How can G-protein diversity lead to a specific cellular response?
Activated GPCRs preferentially act with specific types of G protein (mainly determined by alpha subunit type) and the G-protein subunits interact with specific effector proteins.
Extracellular signals work via a specific GPCR, activating a single/sub population of G-proteins and effectors, bringing about a specific response.