Molecular basis of protein action Flashcards
How is polycystic kidney disease an example of loss of control?
PKD are transmembrane proteins required for normal renal tubule development.
They regulate calcium signalling and cell to cell interactions.
Mutations in this produce cystic kidneys.
How is haemophilia an example of losing control?
Genetic deficiency in clotting factor VIII, causes increased bleeding.
Arises from spontaneous mutations in X chromosomes.
What is a linear enzyme pathway?
Enzyme 1 signals to enzyme 2, 3, 4, and 5.
very simple
What are amplifying enzyme pathways?
Enzyme 1 could signal to 2 enzyme 2s, which then amplify to 2 enzyme 3s.
Each enzyme might act in isolation.
What is a multi-protein complex?
80 proteins in ribosome bound with RNA.
Proteins are bound so do not act in isolation.
How are proteins controlled through expression?
Regulates how much protein there is:
An enzyme could be rate limiting - can control the whole pathway by controlling how much of one enzyme there is.
Could drive transcription, and therefore protein synthesis.
How are proteins controlled through degradation?
Could shut down protein formation by dampening transcription.
Or a protein might be degraded, proteins are cut up by proteases - post transcriptional control.
How are proteins controlled through effector ligand binding?
Binding of an effector molecule induces a conformational change that activates or inhibits.
e.g. a proton (changes pH) or another protein.
How do effector ligands bind?
Can bind to active site as a competitive inhibitor.
Or bind somewhere else, and can regulate conformation - of allosteric proteins.
Allosteric proteins may have multiple ligand binding sites.
What is inhibiting allosteric regulation?
A substrate binding to an enzyme might produce an end product, which then binds to another site on the original enzyme.
This changes the conformation of the enzyme so it no longer binds to the substrate, and the end product is not made.
Negative feedback loop.
What is an example of negative allosteric regulation?
Threonine is acted on by threonine deaminase to produce isoleucine.
When activity is high, lots of isoleucine is produced, it reaches a threshold and binds effectively to threonine deaminase.
This changes conformation of threonine deaminase so less is produced.
What is activating allosteric regulation?
Inactive pKA, held by regulatory subunits.
As the concentration of subunit rises, cAMP can bind to subunit, changes the conformation of regulatory subunit, so catalytic subunit becomes active.
What is cooperative binding of allosteric regulation?
The binding of oxygen to haemoglobin subunits causes a conformational change of the other subunits which increases their affinity for oxygen.
Oxygen dissociation curve is sigmoidal curve.
How does pH control proteins?
When acidic, ionisable groups can become protonated.
Catalytic Aspartate residues in proteases undergo conformational change.
What is pH control in Cathepsin D?
Cathepsin D enzyme is found in acidic endosomal compartments.
When acidic, the N-terminal peptide interacts with protons so the active site is open.
If cathepsin D leaks out into cytoplasm, pH is higher, the structure returns to closed, so is inactive.
