Proteoglycans Flashcards
T or F: proteoglycans form a hydrated gel
True
What are 2 mainfunctions of proteoglycans?
- Shock Absorber
2. Joint Lubricator
What are the component parts of a proteoglycan?
- Core Protein
2. Repeating (GAG) disachharide
What is a GAG?
- General Name for a disaccharide containing a and acidic sugar to one containing an amino group.
T or F: proteoglycans are polycations?
False, they are polyanions
What give proteoglycans their cushiony properties?
- Polyanion GAG segments are attached to a core protein
- Na+ and H2O bind to the polyanions
- Na+ and H20 are squeezed out under pressure and are drawn back in when the pressure is removed
What type of bond joins glycoaminoglycans (GAGs) to the core protein?
Covalent
T or F: the level of hydration of GAGs gives them a large mass relative to their volume.
False, they have a large volume relative to their mass
How do proteoglycans use their anionic charge to interact with matrix proteins?
- They find proteins with basic amino acids that are POSITIVELY charged
Sequence:
X-X-B-B-X-B-X
**B= Arginine or Lysine
T or F: the inflexible nature of proteoglycans gives them a large volume relative to their mass.
True
A large amount of proteoglycans interact with collagen so what can you infer about the charge and residues that must be present in the collagen protein?
- Positive Residue
2. Has the BBXB sequence where B = Arg or Lys
What kind of linkages link GAGs to the core protein of proteoglycans?
- residue?
- O-glycosidic links to Serine
What often happens to GAGs to increase their negative charge?
- They are sulfated or Acetylated
T or F: a single GAG chain may contain many different types of disaccharide
False, each GAG chain only has ONE type of disaccharide
If only a single disaccharide type can be present in each GAG chain, then how can Chondroitin Sulfate and Keratin Sulfate be attached to the same core protein.
- Chondroitin Sulfate and Keratin Sulfate make up PURE GAG chains containing only that disaccharide type
- Different GAG chains can be present on the same core protein as long as each GAG chain is pure
What type of GAG is NOT covalently attached to a protein?
- sulfated?
- Where is it found?
Hyaluronate - not associated with a protein
- NOT sulfated
Found in:
- Cartilage
- Vitreous humor
What types of GAGs ARE covalently attached to a protein (4 types)?
- type of linkage
- Sulfated?
Types:
- Chondroitin Sulfate
- Dermatin Sulfate
- Heparin
- Heparin Sulfate
Linkage Type:
- Serine and
- link Xyl-Gal-Gal (trisaccharide)
Sulfated?
- YES
Where can you find:
- Chondriotin Sulfate
- Dermatin Sulfate
- Heparin
- Heparin Sulfate
Found in CT and cell surfaces
What sequence is needed for O-Glycosylation?
- how does this differ from N-glycosylation?
Asp/Glu - X - Ser - Gly
- The repeat dissacharide GROWs from the Serine rather than a whole group getting transferred from Dolichol
What is used to grow the glycosyl chain on GAGs?
UDP-sugars
**Note: these are activated intermediates that cost at least 1 ATP a piece
What is PAPS?
Activated sulfate that can be used to make glycoprotein (ATP needs to make PAPS)
What links the serine from the ASP/GLU-X-SER-GLY to the GAG?
- A link Trissacharide (e.g. Gal-Gal-Xyl)
What links proteins like keratin and collagen to proteins like Aggrecan?
- Link Proteins
NOTE: BXBB sequences are for GAG to core protein, not for collagen to aggrecan
What FGF (fibroblast growth factor) a proteoglycan do?
Stores Growth Factors so that they are readily available when they need to be used
What is heparin sulfate + growth factor?
Fibroblast Growth Factor
***Important in wound healing etc.
Why would you ever want a cell surface proteoglycan (bound in cell membrane) near an integrin protein?
- It can bind integrin protein and make EXTRAcellular proteins like fibronectin compete to bind
- This fine tunes matrix-cell interactions
T or F: because of their capacity for making multiple interactions proteoglycans can act as more than just shock absorbers
True, They can interact with Proteins, growth factors, and cells
**All purpose velcro
What are the 3 components of aggregating proteoglycans?
- Proteoglycan Monomers
- Link Protein
- Hyaluronate
T or F: glycoproteins can act as cell receptors that can bind and cause change within the cell or be internalized along with their ligand
True, these proteoglycans can be integral membrane proteins or they can may be associated through covalent bonds to membrane lipids etc.
What is Mucosaccharidosis?
- how is it detected?
- Deficiency in recylcing and degradation of GAG polysaccharids and mucolipids
- Patients accumulate GAG and it is PRESENT IN URINE
What are 6 syndromes that result from Mucosaccharidosis?
- Hunter Syndrome
- Hurler Syndrome
- Scheie Syndrome
- Sanfillipo A, B, C
- Mucolipidosis VII
- Tay-Sachs
If a proteoglycan core protein is internalized as part of its receptor function what happens to the GAG?
- It is degraded
