Post-translational modifications - week 2 Flashcards
What is post translational modification?
the modification of selected residues in a protein after it has been made but not as part of synthesis
Where do some posttranslational modifications take place?
ont he nascent chain
name for examples of PTM
- acetylation
- hydroxylation
- glycosylation
- phosphorylation
What is acetylation?
- addition of acetyl group
- mostly at N-terminal
- only found in eukaryotes - not in mitochondria and chloroplasts
can lysine residues be acetylated within the protein?
yes - gamma amino group
How may cytoplasmic proteins are acetylated?
around 60 to 90%
what does acetylation involve?
transfer of acetyl group from cofactor acetyl coenzyme A
- done by acetyltransferase enzyme
What proteins do most often become N-Terminally acetylated?
structural proteins such as keratin
What does N-term acetylation do?
- protects proteins form degradation by amino peptidases
- increases half-life of proteins form seconds to hours or days
Can histones be acetylated?
yes,
- lysine residues in histone proteins are often acetylated
- associated with histones born to transcriptionally active DNA
What is result of histone acetylation?
- reduces net positive charge between histones and DNA leading to more open confirmation and more transcriptional activity
What do histone deacytalases (HDACs) do?
remove modification leading to a closed nucleosome conformation with no transcriptional activity
What is hydroxylation?
- the addition of an OH group
What residues can be hydroxylated?
proline -> hydroxyproline
lysine -> hydroxylysine
What does hydroxylation do?
- hydroxyl groups can form hydrogen bonds with water molecules
- hydroxylation of organic compounds converts hydrophobic molecules into hydrophilic molecules
What is a major component of collagen?
hydroxyproline (hydroxylysiine also present)
What does hydropproline do?
involved in H bonding within collagen fibre which is key for its structural stability
What do you call the enzyme that converts porcine to hydroxyproline ?
prolyl hydroxylase
What is required by prolyl hydroxylate as a cofactor?
ascorbic acid (vitamin C)
What is the connection between hydroxylation and collagen?
- collagen sequences has GXY repeat
- porcine is often found in X position
- 15-30% of proline is in hydroxyproline form, normally in the Y position
What is glycosylation?
the attachment of sugar molecules to specific residues in proteins
Where does glycosylation take place?
- only in eukaryotes
- in lumen of ER and in Golgi
What does sugar make proteins?
more soluble
What is the effect of some glycosylations to proteins?
makes them prone to degradation
What proteins are often glycosylated?
proteins that are secreted form cells
What are the two major forms of glycosylation?
- N-glyosylation
- O-glycosylation
what is N glycosylation?
- involves attachment of a preformed complex carbohydrate (oligosaccharide) molecule to nitrogen of an asparagine residue
Where does N-glycosylation occur?
in a sequence N-X-S/T except where X is proline
What does the oligosaccharide initially consist of in N glycosylation?
- 2 molecules of glucosamine,
- 9 molecules of mannose
- 3 molecules of glucose
What does O glycosylation involve?
- the attachment of sugar to O group of threonine and serine
- no characteristic sequence involved
what is one of the most common forms of PTM?
phosphorylation
Where does phosphorylation occur?
in prokaryotes and eukaryotes
Is phosphorylation reversible?
yes
What happens during phosphorylation ?
hospjhoryl group (derived form ATP) attached to the OH in the side chains of threonine, serine, thyrosine
What attaches phosphate groups to proteins?
enzymes called kinases
What removes phosphate groups from proteins?
phosphatases
What is the role of a phosphate group?
- carries 2 negative charges
- can cause significant change in protein structure and activity
Kinases can be very selective, give an example of one
Protein Kinase A - modifies at R-R-X1-S/T-X2 where X1 is a small residue and X2 is a large hydrophobic residue
Name other examples of PTM
- nucleotide addition
- carbonylaiton
- Sulfonylation
