G Proteins Flashcards
What are the different types of receptors?
Cell Surface:
- Ion channels
- G-Protein coupled receptors
- Enzyme coupled receptors
Cytoplasmic/nuclear:
-Nuclear receptor superfamily
How do G Protein coupled receptors work?
- Ligand bind to G Protein coupled receptor
- Activates an intracellular G-Protein which in turn activates an enzyme which changes the concentration of an intracellular second messenger (eg, cAMP)
What is the structure of a G Protein?
A nucleotide (guanosine trophosphate)
Three phosphates
Ribose sugars
Guanine base
Alternates between GTP and GDP
How do GTP binding proteins work?
- Always inactive when GDP is present
- Always active when GTP is present
- Instead of the addition of a phosphate, the entire GDP molecule is removed and replaced by a GTP
- GTP can be hydrolysed very quickly
What are the two types of G Proteins?
- Monomeric
- Trimeric
How do monomeric G proteins work?
- GEFs (Guanine nucleotide exchange factors) activate G Protein encouraging it to release GDP
- Each G protein has their own specific GEF
- GAP (GTPase Activating Proteins) increases the activity to hydrolyse GTP into GDP
most monomeric G Proteins are often involved in more complex pathway
What is Ras?
A monomeric GTPase
What are the structure of trimeric G Proteins?
Three subunits:
- alpha (50kD)
- beta (35kD)
- gamma (8kD)
beta and gamma subunits are tightly complexed
What do trimeric proteins do?
Relay signals from G Protein coupled receptors
- G Protein is attached to the cytoplasmic face of the plasma membrane
- Alpha and gamma sub units have covalently attached lipid molecules that aid in binding to the plasma membrane
- Activation of G Protein, via receptor activation
- Inactivation of G Protein by GTP hydrolysis by alpha subunit
What are the characteristics of G-Protein Coupled Receptors (GPCRs)?
Seven transmembrane alpha helical regions
- four extracellular regions
- four cytosolic regions
C3 loop is the exchanger of GDP so a key part of the receptor
What is the timeric G Protein activated by?
An activated GPCR
- Binding of ligand to GPCR changes the shape of the receptor
- Allows GDP to be exchanged for GTP
- Alpha and beta subunits may dissociate and elicit a second messenger system
What is cAMP?
cAMP is produced from ATP by adenylyl cyclase, releasing pyrophosphate
it is cyclic due to the carbon bonding on the ribose sugar to two oxygen molecules
What is the effect of cAMP?
-Active cAMP-dependent protein kinases (PKA) which exist in inactive form but binding of cAMP causes dissociation of regulatory subunits
What is the effect of activated PKA?
PKA can phosphorylate target proteins eg, metabolic enzymes in glycogen metabolism
Alter gene transcription via cyclic AMP response element binding protein (CREB)
What happens when there is increased cAMP?
Glycogen breakdown can stimulate PKA when increased cAMP is present and it can inhibit the glycogen synthesis and more cascade reactions
