G protein linked receptor signalling Flashcards
What kind of molecules do receptors on the plasma membrane bind
Hydrophilic
What is the largest family of cell surface receptors?
And what processes do these receptors mediate?
G proteins
Metabolism, learning, memory, olfaction, vision
What is the common structure of the 7 transmembrane passes?
Extracellular ligand binding domain, intracellular G protein binding domain
What is the first messanger?
The ligand for the receptor
Describe G protein linked receptors
7 transmembrane helices H1 -> H7
Not every transmembrane receptor is coupled to a G protein, but all G proteins bind to 7 transmembrane receptors
What is the second messanger?
Molecule produced inside a cell in response to activation
Adrenaline and G protein receptors
Adrenaline binds to the beta-adrenergic receptor. The beta-adrenergic receptor is coupled to a G protein which consists of 3 domains: alpha, beta and gamma. Beta and gamma never separate and are always bound.
The alpha subunit can separate from the beta, gamma pair.
The alpha subunit can bind to guanine nucleotide (GDP or GTP)
The alpha and gamma subunits are attached to the plasma membrane.
Activating the G protein of a beta-adrenergic receptor
7-TM is activated and permits the exchange of GTP for GDP activating the G protein. The alpha subunit leaves the binding pair and goes off to activate other molecules (adenyl cyclase)
G protein activation cycle (6 steps)
- Binding of hormone induces a conformational change in the receptor
- Activated receptor binds G-alpha subunit
- Activated receptor causes conformational change in G-alpha triggering dissociation of GDP
- Binding of GTP to G-alpha triggers dissociation of G-alpha from the receptor and G-beta-gamma
- The hormone dissociates from the receptor. G-alpha binds to effector activating it
- Hydrolysis of GTP to GDP causes G-alpha to dissociate from the effector and associate back with the G protein complex.
Why is the G protein heterotrimeric?
Has 3 subunits
Describe the off state of the G protein
Inactive, heterotrimeric (alpha, beta, gamma)
alpha subunit bound to GDP
Cell signalling in the ovary
Luteinising hormone
Progesterone secretion
Cell signalling in the muscle
Adrenaline
Glycogen break down
Cell signalling in the kidney
Vasopressin
Water re-absorption
What synthesises cAMP
Enzyme adenyl cyclase converts ATP to cAMP
What degrades cAMP?
cAMP phosphodiesterase
Provide an example of a secondary messenger
cAMP
What is adenyl cyclase regulated by?
G proteins
G-beta-gamma
Ca2+
What is the effect of hormones on adenyl cyclase receptors?
stimulate- epinephrine - receptor coupled to G-alpha-S
inhibit - adenosine - receptor coupled to G-alpha-i
What does cAMP activate?
cAMP-dependent protein kinase (PKA)
EPAC
Are there more molecules of cAMP than starting hormone?
Yes
PKA structure
Heterotetramer
Explain the process that leads to the release of active catalytic subunits of PKA
Inactive PKA is a heterotetramer of 2 regulatory subunits and 2 catalytic subunits. cAMP binds to the regulatory subunits inducing a conformational change allowing the release of active catalytic subunits.
Cellular function dependent on IP3: Pancreas, Skeletal muscle, blood platelets
Pancreas = acetylcholine = amylase secretion
Skeletal muscle = acetylcholine = contraction
Blood platelets = Thrombin = Aggregation
