Post-translational modifications - week 2 Flashcards

1
Q

What is post translational modification?

A

the modification of selected residues in a protein after it has been made but not as part of synthesis

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2
Q

Where do some posttranslational modifications take place?

A

ont he nascent chain

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3
Q

name for examples of PTM

A
  • acetylation
  • hydroxylation
  • glycosylation
  • phosphorylation
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4
Q

What is acetylation?

A
  • addition of acetyl group
  • mostly at N-terminal
  • only found in eukaryotes - not in mitochondria and chloroplasts
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5
Q

can lysine residues be acetylated within the protein?

A

yes - gamma amino group

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6
Q

How may cytoplasmic proteins are acetylated?

A

around 60 to 90%

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7
Q

what does acetylation involve?

A

transfer of acetyl group from cofactor acetyl coenzyme A
- done by acetyltransferase enzyme

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8
Q

What proteins do most often become N-Terminally acetylated?

A

structural proteins such as keratin

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9
Q

What does N-term acetylation do?

A
  • protects proteins form degradation by amino peptidases
  • increases half-life of proteins form seconds to hours or days
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10
Q

Can histones be acetylated?

A

yes,
- lysine residues in histone proteins are often acetylated
- associated with histones born to transcriptionally active DNA

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11
Q

What is result of histone acetylation?

A
  • reduces net positive charge between histones and DNA leading to more open confirmation and more transcriptional activity
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12
Q

What do histone deacytalases (HDACs) do?

A

remove modification leading to a closed nucleosome conformation with no transcriptional activity

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13
Q

What is hydroxylation?

A
  • the addition of an OH group
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14
Q

What residues can be hydroxylated?

A

proline -> hydroxyproline
lysine -> hydroxylysine

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15
Q

What does hydroxylation do?

A
  • hydroxyl groups can form hydrogen bonds with water molecules
  • hydroxylation of organic compounds converts hydrophobic molecules into hydrophilic molecules
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16
Q

What is a major component of collagen?

A

hydroxyproline (hydroxylysiine also present)

17
Q

What does hydropproline do?

A

involved in H bonding within collagen fibre which is key for its structural stability

18
Q

What do you call the enzyme that converts porcine to hydroxyproline ?

A

prolyl hydroxylase

19
Q

What is required by prolyl hydroxylate as a cofactor?

A

ascorbic acid (vitamin C)

20
Q

What is the connection between hydroxylation and collagen?

A
  • 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
21
Q

What is glycosylation?

A

the attachment of sugar molecules to specific residues in proteins

22
Q

Where does glycosylation take place?

A
  • only in eukaryotes
  • in lumen of ER and in Golgi
23
Q

What does sugar make proteins?

A

more soluble

24
Q

What is the effect of some glycosylations to proteins?

A

makes them prone to degradation

25
Q

What proteins are often glycosylated?

A

proteins that are secreted form cells

26
Q

What are the two major forms of glycosylation?

A
  • N-glyosylation
  • O-glycosylation
27
Q

what is N glycosylation?

A
  • involves attachment of a preformed complex carbohydrate (oligosaccharide) molecule to nitrogen of an asparagine residue
28
Q

Where does N-glycosylation occur?

A

in a sequence N-X-S/T except where X is proline

29
Q

What does the oligosaccharide initially consist of in N glycosylation?

A
  • 2 molecules of glucosamine,
  • 9 molecules of mannose
  • 3 molecules of glucose
30
Q

What does O glycosylation involve?

A
  • the attachment of sugar to O group of threonine and serine
  • no characteristic sequence involved
31
Q

what is one of the most common forms of PTM?

A

phosphorylation

32
Q

Where does phosphorylation occur?

A

in prokaryotes and eukaryotes

33
Q

Is phosphorylation reversible?

A

yes

34
Q

What happens during phosphorylation ?

A

hospjhoryl group (derived form ATP) attached to the OH in the side chains of threonine, serine, thyrosine

35
Q

What attaches phosphate groups to proteins?

A

enzymes called kinases

36
Q

What removes phosphate groups from proteins?

A

phosphatases

37
Q

What is the role of a phosphate group?

A
  • carries 2 negative charges
  • can cause significant change in protein structure and activity
38
Q

Kinases can be very selective, give an example of one

A

Protein Kinase A - modifies at R-R-X1-S/T-X2 where X1 is a small residue and X2 is a large hydrophobic residue

39
Q

Name other examples of PTM

A
  • nucleotide addition
  • carbonylaiton
  • Sulfonylation