Post-Translational Modifications

Question 1

What are the 2 major types of glycosylation?

Answer 1

N- linked

O- linked

Question 2

Describe N-glycosylation

Answer 2

it is not a true PTM but it occurs in the ER and involves attachment of a pre-cursor glycan structure added to the peptide chain. It occurs as the peptide is translocated off the ribosome into the ER

Question 3

What is the function of the N-linked glycan?

Answer 3

Protein folding
Disulphide bond formation stability
Solubility
Protection from proteolysis
Clearance

Question 4

Describe O-linked glycosylation

Answer 4

A true PTM - occurs in golgi body

involves attachment of N-acetyl-glycan residues to a serine or threonine

Question 5

What are the functions of O-glycosylation?

Answer 5

Not entirely understood
provides stability to flexible regions of proteins
may have roles in clearnce and ligand recognition

Question 6

How many N-linked sites are there in vwf?

Answer 6

16

Question 7

How many O-linked sites are there in vwf?

Answer 7

10

Question 8

Why is N-linked glycosylation of vwf essential?

Answer 8

Lack of n-linked glycosylation leads to intracellular retention of vwf monomers
n-linked glycosylation in the CK knot is required for efficient dimer formation

Question 9

What does the vwf display on its n-linked glycans?

Answer 9

ABO blood group

this mediates vwf clearance

Question 10

What do the ABO sugars on vwf modulate?

Answer 10

They modulate cleavage by ADAMTS13

Question 11

Where are the O-linked glycosylation sites on vwf? And what is this domain important for?

Answer 11

They are clustered around the A1 domain

It is important for platelet binding - it modulates GP1b binding

Question 12

What is glycosylation in FVII important for?

Answer 12

secretion on FVII

Question 13

Is FVIII glycosylated?

Answer 13

It is heavily glycosylated on the B domain