Signalling principles Flashcards
How do ligands act at low Kd?
High affinity
Background levels of ligand bind the receptor
High on rate or slow off rate
How do ligands act at high Kd?
Weak ligand binding
Requires high concentrations for a signal
What is the optimal ligand concentration roughly?
Kd
How are receptors inactivated?
Ligands actively removed
Receptor internalisation
Deactivating receptor via arresting
Degradation by enzymes
Explain avidity
If a ligand binds with two weak interactions, a strong ligand can block rebinding
Strong ligand has a slow off rate, allowing the ligand to dissociate
Why can proteins switching to the wrong conformation be problematic?
Constitutive switching on can lead to cancers
How can receptor activation be turned from hyperbolic to sigmoidal?
Whack in a kinase cascade
Why is colocation important in signalling?
Happens in the same place for switch-like behaviour and amplify the signal. Makes signalling quicker.
Lengths of linker proteins affects amounts of collisions
What makes a good signal?
Released in appropriate quantities to be detected by correct receptor
Small enough to travel easily
Synthesised and sequestered easily
Appropriate Kd
How are kinases switched off?
Binding of B-arrestin
Internalisation
Phosphatases linked by scaffolds
Ubiquitibation and degradation
How are G-proteins switched off?
GTPase activating proteins
Arrestin and B-adrenergic receptor kinase
Enzymes to degrade substrate
