Signal transduction and biological membranes Flashcards
What is a G protein and what is its mechanism of action?
They are a family of receptors which activate a number of G proteins to alter the activity of effectors e.g. enzymes. They are made up of three distinct subunits (alpha, gamma, beta).
- Agonist binds receptor
- Protein-Protein interaction releases GDP, binds GTP
- GTP and alpha/ beta subunit released and interact with effectors
- GTP hydrolysed to GDP
- GDP and subunits reform heterotrimer
What are the cellular targets for activated G proteins?
Gs - adenylyl cyclase
Gq - phospholipase C
Gi - adenylyl cyclase
Gt - stimulates cyclic GMP
What is the effect of ligand binding?
Ligands bind very specifically to receptors. When it binds it activates the receptor, bringing about a change in cellular activity.
What is the difference between an agonist and an antagonist?
Agonists bind to the receptor and activate it. Antagonists bind to the receptor but to not activate it. They prevent the binding of agonists.
Discuss the diversity of G proteins
The human genome codes for multiple alpha, beta and gamma subunits - therefore there are over 1000 possible combinations. Around 800 have been identified.
Describe some common diseases associated with GPCRs
Genetic mutations can result in loss of function or gain in function
- Retinitus pigmentosa: loss of function to Rhodopsin
- Nephrogenic Diabetes Insipidus: V2 vasopressin
- Familial male precocious puberty: gain in function of LH receptor
Summarise the effectors for Gs, Gi and Gq
Gs stimulates the hydrolysis of ATP and the production of cyclic AMP.
Gi inhibits the production of cyclic AMP
Gq activates phospholipase C which hydrolyses the membrane PIP2 to IP3. This increases cytoplasmic calcium concentration.
How are GPCR signals ‘switched off’?
The alpha-GTP interaction with effectors lasts until the alpha subunit GTPase activity hydrolyses GTP back to GDP. the alpha GDP and beta-gamma subunits then reform an inactive heterotrimeric complex.
