Intracellular Proteolysis Flashcards
What is proteolysis?
The opposite of protein synthesis- break down of proteins using hydrolysis reactions
What’s a synonym for proteases?
Peptidases
What do serine proteases contain at their active sites?
Serine
What do cysteine and aspartyl proteases have at their active sites?
Aspartic acid residues
What must metalloproteases form a compound with in order to be activated?
Specific metal ions
What’s the difference between endopeptidases and exopeptidases?
Endopeptidases are used in the middle of the protein chains and exopeptidases are used on the ends of protein chains
If the sequence of proteolysis is specific, what happens to the protein?
It is activated
If the sequence of proteolysis is non-specific, what happens to the protein?
Degraded
What gives rise to multiple peptide hormones?
Proteolytic processing of propiomelanocortin in the Golgi apparatus
Give examples of cysteine proteases
Bromelain (pineapples)
Papain (papaya)
How do cysteine proteases work as meat tenderisers?
meat is Mostly protein and proteases help break down the tough fibres
Give an example of an aspartyl protease
HIV-1 protease (AKA retropepsin) catalysed the cleaving of the long precursor chain on HIV which activates it
Why is non-specific protein degradation compartmentalised?
To stop it causing lots of damage in other parts of the cell
What are the two pathways proteins could follow to be degraded?
Lysosomal or ubiquitinproteasome
How are proteases formed in the lysosomes designed to minimise damage?
They only operate at low pHs
What are the steps in the protein degradation pathway of ubiquitinproteasome?
- protein is first covalently modified with a chain of ubiquitin molecules
- it is then targeted to the proteasome structure
What molecule attaches to a molecule to mark it for proteasomal degradation?
Ubiquitin
What is the 3 step pathway for protein ubiquitylation
1- ubiquitin is attached to E1 which reacts with the COOH via the cysteine residue. This requires ATP and forms a thioester bond
2- ubiquitin is attached to E2 also via a thioester bond
3- the ubiquitin-E2 complex has E3 added to it. Then it is transferred from the cysteine to the lysine residue.
Which residues have to be polyubiquitinated for them to be marked for proteasomal degradation
K11 or k48
Why do some proteins have a long half life and some have a short half life?
Depends on the amino acid at the N-terminus of the amino acid. Stabilising amino acids are not well recognised by the ligases so will survive longer and vice versa
