GPCRs Flashcards
What are the subfamilies of GTPases?
Small; eg Ras, Rac, Rho
Large; eg dynamin
Translational; eg EF-Tu, eIF2
Heterotrimeric; G proteins
What are G proteins made of?
Alpha subunit
Beta subunit
Gamma subunit
What is meant when it is said that G proteins are functionally dimeric?
Despite having three subunits, the beta and gamma never split.
What are the G protein subunits responsible for?
Both; receptor recognition, effector recognition
Alpha; GTPase activity, interaction with regulatory proteins eg RGS
BetaGamma; High affinity for GDP-bound alpha subunit.
What is a GEF
A guanine nucleotide exchange factor
Describe the GPCR cycle
1) When GDP is bound, the G protein is a heterotrimer and inactive
2) GPCR acts as a GEF, promoting GTP-for-GDP exchange
3) G-beta-gamma subunits lose affinity for G-alpha-GTP, so dissociate.
4) G-beta-gamma and G-alpha-GTP interact with effectors
5) G-alpha-GTP undergoes GTP for GDP exchange and loses regulatory activity
6) G-alpha-GDP and G-beta-gamma re-associate
How many types of G protein subunit are there?
Many; alpha has 17-20 in total inc s, i/o, q/11, 12/13; beta has 1-5; gamma has 1-13
Give examples of the effectors with which G-alpha subunits can interact
Adenylyl cyclase activation and inhibition
PLC activation
Ion channel modulation
What do i/o type G proteins do?
Inhibit adenylyl cyclase. Reduces production of cAMP, which inhibits PKA activities and reduces calcium influx
What do q type G proteins do?
Interact with PLC, which then will cleave PIP2 into IP3 and DAG. This alters calcium.
What do S type G proteins do?
Activate Adenylyl cyclase. Increases production of cAMP, which activates PKA and affects calcium.
What does homologous desensitisation mean?
Where the attenuation in the signalling response is specific to the receptor being simulated
What does heterologous desensitisation mean?
where “collateral” receptor signalling (i.e. responses stimulated/inhibited by receptors not directly exposed to agonist stimulation) is also desensitised.
