Lecture 5 Flashcards
(9 cards)
What are the three super families of cell surface receptors?
G protein coupled
Receptors with intrinsic enzymatic activity
Ligand gated ion channels
G protein coupled receptor structure?
Single polypeptide chain with seven trans membrane spanning domains
Extracellular N terminus and intracellular C terminus
Where do ligand bind to G protein coupled receptors?
Some bind between a few of the transmembrane spanning domains while other bigger ligand can bind to the N terminus.
How does a G protein coupled receptor cause a change in cellular activity?
Operates under the receptor-transducer-effector mechanism.
On ligand binding the receptor undergoes a conformational change. the receptor is bound to a G protein which is heterotrimeric meaning that it consists of three subunits alpha, beta and gamma. The alpha subunit has a GDP attached and has GTPase activity. On ligand binding the GDP bound to the alpha subunit is swapped for a GTP. This results in the alpha subunit separating from the beta and gamma subunits. These act as transducers which then go on to activate various effectors. After a while the GTPase activity of the alpha subunit causes the hydrolysis of the GTP back to GDP and P and this causes the subunits to reassociate and become inactivated. If GTPase activity is increased the effects it activation of the receptor result in will cease quicker.
How can different cellular responses be generated by one G protein coupled receptor?
On activation it can transducer the signal through different G proteins that have different activity. For example when adrenaline acts on a beta adrenoreceptor it activates alpha s and causes and excitatory response, adenylyl cyclise is activated which in turn activates cyclic AMP. Alpha i causes an inhibitory response where cyclic AM is inhibited.
How can you interfere with GPCR’s
Using pertussis toxin and cholera toxin.
Pertussis works on the Gi alpha subunits by preventing GTP GDP exchange and locking subunit into inactive state.
Cholera toxin works by preventing hydrolysis of the alpha s GTP and maintains it in the active state
Why is pertussis and cholera toxin important?
For the study of GPCR’s
What does G alpha q lead to
Activation of phospholipase C which in turn activates DAG and IP3. IP3 leads to ca2+ release and phospholipase C binds protein kinase C and leads to protein phosphorylation.
How does signal amplification work?
Gs activates adenylyl cyclase which activates many cAMP which in turn activate many protein kinases.
