Flashcards in deck_782667 Deck (42)
What are G protein coupled receptors?
A family of receptors that act by altering the activity of effectors
What do G-proteins activate in order to interact with effectors?
Gunaine nucleotide binding proteins
What is the the word to describe G-proteins?
How can G-proteins be described as heterotrimeric?
The consist of three different subunits - alpha, beta and gamma- Beta and gamma bind tightly together and form single unit- Alpha has a GTP binding site which has GTPase activity (slowly hydrolyses bound GTP to GDP)
Where is the G-protein usually present in the cell, and in what form?
at the inner face of the plasma membrane
Describe what occurs when G-protein coupled receptor binds an agonist
Agonist binds receptorProtein-Protein interaction releases GDP, binds GTP to alpha subunita-GTP and bg released and interact with effectorsGTP hydrolysed to GDPa-GDP and bg reform heterotrimer
What is the interaction of G proteins with effectors inhibited by?
Intrinsic GTPase activity of alpha subunit. Once bound GTP hydrolysed to GDP, the affinity of alpha subunit for bg increases, and the hetertotrimer reforms
How g proteins be thought of a switches and timers?
The on switch is receptor-facilitated GDP/GTP exchangethe timer/off switch is governed by the length of time taken for GTP hydrolysis.
What is the role of stimulatory G (Gs) proteins?
Plays an intermediate role - stimulate adenylyl cyclase to produce cAMP
What is the role of inhibitory G protein (Gi) paths?
Inhibit adenylyl cyclase, reducing cAMP Also effect ion channels and signalling pathways involved in growth and differntiation
What do Gq proteins interact with?
Activate phospholipase C, which hydrolyses PIP2 to IP3
What is the name of the light sensing receptor in the eye, and what does it activate?
Rhodopsin, activates Gt whichin turn activates a phosphodiesterase enzyme that hydrolyses cyclic GMP to 5'-GMP
What does adrenaline activate when activating b adrenoreceptors? Receptor, G protein, effects, physiological response
b-AdrenoceptorGsStimulates Adenylyl CyclaseGlycogenolysis, lipolysis
What does acetylcholine activate when interacting with M3?
GqStimulates Phospholipase CSmooth Muscle Contraction
What does Ach activate when interacting with M2?
GiInhibits Adenylyl CyclaseStimulates K+ ChannelSlowing of Cardiac Pacemaker
What does light do?
RhodopsinGtStimulates Cyclic GMP PhosphodiesteraseVisual Excitation
What G protein and effector do the following use?a1a2
a1 - Gq, stimulate phospholipase Ca2 - Gi, inhibit adenylyl cyclase
What G protein and effector do the following use?b1b2
b - Gs, stimulate adenylyl cylase
What G protein and effector do the following use?M1M2M3
M1 + M3 - Gq, stimulate phospholipase C,M2 - Gi, inhibit adenylyl cyclase
How many Ga, Gb and Gg exist?
20 Ga, 5Gb and 12+ Gg proteins.
How may possible Ga, Gb and Gg combinations are there?
How many receptor types are there, and what do they interact with?
800 receptor types, which can interact with different G subtypes to activate/inhibit 10 or more enzyme/ion channel effectors.
What do Cholera (CTx) and Petussis (PTx) toxin do the G protein cycle?
enzymes that ADP-Ribosylate specific G-Proteins
What does CTx do?
Eliminates the GTPase activity of Gsa, leading it to become irreversibly activated (opening chloride ion channels!)
What does PTx do?
PTx interferes with the GDP/GTP exchange on Gia. This leads Gia to become irreversibly inactivated.
What can genetic changes to GPCRs cause?
loss-of-function or gain-of-function mutations
How is retinitis Pigmentosa caused?
By a loss-of-function mutation to Rhodopsin
What are the symptoms of retinitis pigmentosa?
Severe visual impairment
How is nephrogenic diabetes insipidus cause?
By a loss-of-function mutation to V2 Vasopressin receptor