9: Post-translation And Regulation Flashcards
Briefly describe the general process in a cell between signalling ad the cell response?
- A first messenger signalling molecule binds to a receptor on the cell membrane, or inside the cell.
- Second messenger molecules relay the message through the cytoplasm. This is the process of transduction
- An active effector (eg TF) allows a gene to be transcribed. This is the response
List some examples of post-translational modifications
- Methylation, acetylation, myrisoylation
- Ubiquitination
- Glyosylation
- Disulfide-bridge
- Phosphorylation
- Truncation
- Protein-protein interactions
How does post translational modifications affect proteasome complexity?
P increases proteasome complexity
It increases the proteome to over a million different proteins
What is trimming
Truncation - removal of a part of the protein, mediated by protease
What are some examples of effects on proteins that PTMs can have post-synthesis?
- Can affect the activity of protein
- Folding of protein (interactions)
- Degradation & stability
- Translocation
What is phosphorylation?
The addition of a PO4 phosphate group to a protein/small molecule.
Occurs on serine, threonine, tyrosine
Is protein phosphorylation reversible?
Yes, phophatases can dephosphorylate substrate proteins
What is Ubiquitination?
Addition of one or several ubiquitin molecules to a target protein.
Results in the highly specific degradation of a protein
Which enzymes carry out ubiquitylation
E1, E2, and E3 enzymes
Which enzyme carries out the degradation of the ubiquitin proteasome system?
26S proteasome enzyme
Which enzymes carry out de-ubiquitylation?
DUBs - de-ubiquitylation enzymes
Briefly describe the process of ubiquitylation
1: Activation - Ub is activated by E1 enzyme in ATP-dependent reaction. Ub is conjugated to E1.
2: Conjugation - Activated Ub is transferred to E2, forming thioester bond
3: Ligation - E3 Ub ligase recognises & binds to target protein. E3 ligase facilitates transfer of Ub from E2 -> target protein.
4: Polyubiquitylation - Sometimes, multiple Ub are added to target protein. Occurs through attachment of Ub to a lysine residue. Different polyUb chains have different cellular consequences depending on what lysine residue it is added to.
5: Degradation/Regulation - Some Ub modifications result in the degradation of the attached target protein, others can affect protein localization, interactions, or activity.
What happens if a K48-linked poly ubiquitin chain is added?
Attached target protein is targeted for degradation by the proteasome
What is ubiquitin resistant to
Heat, pH extremes, and proteolysis
How many amino acids are in Ubiquitin?
76
