PT!M

Question 1

What is special about MUc1?

Answer 1

Has a tandem repeat sequence with 5 potential sites for O-linked glycosylation
3 glycosyltransferases needed for all five sites.
Used as model to study substrate specificity & kinetics of glucosylyransferases.

Question 2

Outline mucin type O-linked glycosylation.

Answer 2

Sugars added to Ser & Thr linked through O
Sugars added singly & catalysed by glycosyltransferases
First added sugar is GalNAc
Initiation is in Golgi.

Question 3

What is the equation for the addition of the first sugar?

Answer 3

UDPGalNAc + Thr/Ser-R

–>

UDP + GalNAc-Thr/Ser-R

Many glycosyltransferases can catalyse this.

Question 4

Why can SM3 bind in breast cancers?

Answer 4

Binding blocked by long O-Glycans in normal cells but MUC1 has altered O-Glycans in breast cancer.

Question 5

What sequence are sugars added en bloc in N-linked glucosylation?

Answer 5

Asp-N-Ser/Thr.

Question 6

Which residues are most commonly methylated and which specifically activate and repress chromatin state and gene expression?

Answer 6

Lys or Arg
Histone 3, Lys 27, Methyl 3 (inhibits)
Histone 3, Lys 4, Methyl 3 (activates)

Question 7

What is ubiquitin and what happens if a single one is added?

Answer 7

Highly conserved 76AA polypeptide

Positive Signal.

Question 8

What is Tn syndrome?

Answer 8

Cosmc (private chaperone for T synthase which catalyses formation of core 1 in Golgi) dysfunctional

O-linked glycans expressing only first GalNAc

Question 9

What is significant about BNP?

Answer 9

Synthesised in heart and activated by cleavage (on cardiac myocyte stress) at PRSP sequence
Activation leads to vasodilation.

GalNAcT3 adds GalNAc at particular site inhibiting cleavage at adjacent site (inactive peptide)
Heart doesn’t express T3.