L17 Post-translational Protein Modification Flashcards
What is a proprotein?
An inactive peptide or protein that needs post-translational modifications to be activated
What is post-translational modification?
A proprotein is folded and cut to form its active shape.
e.g. when insulin is being formed, ribosomes feed the growing peptide chain (preproinsulin) into the ER where the signal protein is cleaved by signal peptidase, forming proinsulin.
This is then folded, disulphide bonds are formed and then the C chain is removed to form mature and active insulin.
Why do cells need the capability to modify proteins?
Protein synthesis is limited in it’s abilities - only a relatively limited number of polypeptide chains can be made.
Covalent modifications can expand a protein’s potential by altering its spatial structure and biological activity. Allows for millions of proteins to be made.
Is post-translational modification reversible?
Some PTMs are reversible (e.g. acetylation, phosphorylation and methylation). This allows rapid dynamic regulation of a protein’s activity.
Some PTMs are irreversible.
Post-translational modification:
What is proteolytic cleavage?
Is it reversible?
Cleavage of a protein at a peptide bond.
One or several amino acids could be removed from N-terminus of a protein, or protein peptide bond could be cleaved in the internal part of the protein.
Proteolytic cleavage is irreversible.
Post-translational modification:
What is proline isomerisation?
A change in proline residue spatial conformation (transition between cis- and trans- conformations of peptide bonds involving proline).
Can seriously affect protein structure adopted.
Which enzyme group catalyses phosphorylation?
Kinases
Which enzyme group catalyses dephosphorylation?
Phosphatases
What is controlled by cyclins and their cyclin-dependent kinases?
The cell cycle
Fill in the gaps:
Pyruvate dehydrogenase is regulated by __1__/__2__ by a protein kinase that is __3__ by high [NADH]:[NAD+] and [acetylCoA]:[CoA], and __4__ by pyruvate.
1) phosphorylation
2) dephosphorylation
3) activated
4) inactivated
Give an example of autophosphrylation
EGF pathway - growth factor binds to its receptor and causes the receptor to change shape. The change in shape allows two receptors to come together and phosphorylate one another.
When a tyrosine residue is phosphorylated, what does this promote?
Protein:protein signalling interactions
Complete the sentence:
You can use phospho-specific antibodies and 2-dimension phosphopeptide mapping to __?__.
…detect phosphorylated proteins.
What is protein acetylation?
Protein acetylation is the process in which acetyl group, donated by acetyl Coenzyme A, is transferred to an acceptor amino acid, lysine, in protein.
How is protein acetylation catalysed?
The reaction is catalyzed by a Protein AcetylTransferase (PAT).
Process of a protein deacetylation is catalyzed by a Protein Deacetylase (PDAC).
What proteins are the most characteristic targets of protein acetylation?
Histones.
The histone PATs and PDACs are called histone acetyltransferases (HATs) and histone deacetylases (HDACs).
But they often have non-histone substrates too.
Allows unravelling of DNA for gene transcription.
What is protein methylation?
Protein methylation is the process in which methyl group, donated by S-adenosylmethionine, is transferred to an acceptor protein.
How is protein methylation catalysed?
The reaction is catalyzed by a protein methyltransferase. Process of a protein demethylation is catalyzed by a protein demethylase.
Which 2 amino acids are usually targets for methylation?
Arginine and lysine
Are all protein methylation modifications reversible?
No
What is citrullination?
Citrullination involves altering the chemical nature of arginine, converting it to citrulline (a new amino acid) by removing the N group.
What is a problem associated with citrullination?
Immune system attacks citrullinated proteins - citrullination is implicated as a cause in auto-immune diseases and arthritis.
What is glycosylation?
Addition of mono- and oligo- saccharides to a protein to form a glycoprotein.
Significantly affects protein folding, conformation, distribution, stability and activity.
True or false: most cellular proteins are glycosylated.
True - glycosylation plays numerous biological roles:
stability, trafficking, and recognition
