Intracell Signal Pathway (Receptor/Effector Mechanism) Flashcards
What’re the 3 super families of cell-surface receptor?
G-Protein coupled receptor
Ligand-gated ion channel
Receptor with intrinsic enzymatic activity
What happens when a ligand binds to a receptor?
Ligand binding activates the receptor with in turn directly or indirectly (using transduction) brings about a change in cellular activity
What types of signal molecule can the G-Protein coupled receptor family respond to?
Ions
Neurotransmitters
Peptide and non-peptide hormones
Large glycoproteins
What is the generic basic structure of a G-protein coupled receptor?
Single polypeptide chain
7-transmembrane spanning regions
Extracellular N-terminal
Intracellular C-terminal
How does ligand binding work in G-protein coupled receptors?
2 regions can be responsible for ligand binding.
For some receptors the ligand binding site is formed by some of the transmembrane domains (it binds within the membrane similar to a pore)
For others the N terminal (and other extracellular domains) form the ligand binding site.
How do GPR’s cause a change in cellular activity?
An activated GPCR must interact with another protein called a Guanine-nucleotide binding protein (G protein). The G-Proteins are made up of 3 subunits (alpha, beta + gamma). The alpha unit can attach a GDP or a GTP molecule.
When a receptor binds the a-BY complex dissociates and GDP is swapped for GTP, and each can then interact with an effector. This is the active state.
How is the GPCR returned to its inactive state?
The a-GTP/By interaction with its effectors lasts until the a-GTP is hydrolysed back to a-GDP by GTPase. The a-GTP and By subunits the reform an inactive complex.
How are G proteins diverse?
Activated GPCRs (the membrane bound bit) work with specific types of G protein, the Ga subunit is the primary determinant.
In turn the Ga subunit and By subunit interact with specific effectors.
This allows an intracellular signal to work via a specific GCPR to activate a specific G protein and then a specific effector, to bring about a specific cellular response.
Name 2 toxins that interfere with GPCRs.
And what the can be used for scientifically.
Both cholera toxin and Pertussis toxin work in a simple way. The toxin complex binds to the cell and the enzyme is “injected” into the cell.
Scientifically they can be used to study GPCR-G protein signalling.
Where does the Pertussis toxin interfere with the GPCR process?
It prevents the GDP on the alpha subunit from becoming GTP so the protein doesn’t become activated. Then the signal has no effect even though it has bound.
“It uncouples G-preferring GPCRs from mediating signal transduction events”
How does the cholera toxin interfere with the GPCR signal process?
It prevents the GTP returning to GDP and so the signalling is constantly activated and doesn’t stop.
“It prevents termination of signalling by G-preferring GPCRs leading to long-lasting activation of downstream pathways.
Cholera specifically stimulates cAMP which releases H2O and electrolytes into the gut causing loss of water in diarrhoea.
