Proteolysis - Latency and Activation Flashcards
What are pre-peptides?
Signal peptides responsible in translocation and translation through membranes
Secretory proteins which are synthesised with signal peptides at the N-terminus which is removed after sorting by proteolysis
What are Pro-peptides?
Folding intramolecular chaperones.
These must be removed for activity to occur.
How does latency relate to the secretory pathway?
Most bioactive polypeptides must be inactive whilst in the secretory pathway and then become activated when they are released.
(proteins synthesised in an inactive form)
What does the Trans-Golgi network do?
Sorting of protein and membrane components to constitutive and regulated pathways and to lysosomes.
Cleavage of some pro-proteins also occurs.
What is a secretagogues?
A substance that causes another substance to be secreted.
Where does the constitutive pathways deliver its components to?
The plasma membrane
Where does the regulated pathway deliver its components to?
Forma pool of contents awaiting a secretagogues for release into the cells
What is essential for activation of a protein?
Pro-peptide cleavage.
What do cleavage sites contain?
At least 2 basic residues
What removes the 2 basic residues in cleavage sites after cleavage?
Carboxypeptidase
What are PCSKs?
Proprotein Convertases Subtilisin/Kexin (prohormone converting enzymes)
They are serine proteases and so will cleave at these sites on pro-peptides.
How were PCSKs found?
Found by homology with Kex 2 from yeast.
What was the first mammalian PCSK found and how many are there in total?
First found was Furin (PCSK3)
Currently 9 known mammalian PCSKs
What are the general structure of PCSK genes?
Signal peptide
Prosegment (synthesised in inactive forms)
catalytic domain
P-domain
What is required for PCSK activation?
Synthesised with a prosegment which requires autocatalytic cleavage to activate the PCSK.
What is the role of the P-domain in the PCSK gene?
Regulates the activity of the catalytic domain
Reacts to pH and ion concentration changes.
What do PCSK specifically cleave?
Cleave mostly C-terminal to arg
What amino acids are recognised by PCSKs?
Arg/Lys