What are proteoglycans?
Proteins with glycosaminoglycan (GAG) chains that function on cytoplasmic and extracellular surfaces.
What is a major function of proteoglycans?
Binding specific proteins via their glycosaminoglycan groups.
What type of amino acids are involved in GAG-binding sites?
Basic amino acids like lysine and arginine.
what are common motifs in protein GAG-binding domains?
BBXB and BBBXXB sequences
How does charge affect GAG-protein binding?
Positive charges on proteins neutralize the negative charges of GAGs; more sulfation increases binding.
Can GAG-protein interactions require specific carbohydrate sequences?
Yes, some interactions depend on precise sugar sequences, not just charge.
Give an example of sequence-specific GAG binding.
Heparin pentasaccharide binds antithrombin III, giving anticoagulant properties.
Why is the 3-O-sulfate in heparin important?
It is essential for high-affinity binding to antithrombin III.
Where can proteoglycans be located?
Soluble in the extracellular matrix or as transmembrane proteins.
Give examples of soluble proteoglycans.
Serglycin, versican, cartilage matrix proteoglycan.
Give an example of a transmembrane proteoglycan.
Syndecan.
How do proteoglycans function?
By interacting with molecules through glycosaminoglycan chains and receptor domains.
What does syndecan associate with inside the cell?
The actin cytoskeleton.
What extracellular molecule does syndecan interact with?
Fibronectin.
What roles does syndecan play in the extracellular space?
Acts as a glue, links ECM components, helps cell-matrix binding, mediates growth factor binding.
How can proteoglycans affect cell growth?
They can modulate or regulate cell growth processes.
How do heparin and heparan sulfate influence cell proliferation?
they can inhibit proliferation by internalization and migration to the nucleus.
How do proteoglycans interact with fibroblast growth factor (FGF)?
Bind and protect FGF from degradation, enhancing its activity.
What is the effect of proteoglycans in the ECM on growth factors?
They create a reservoir of growth factors for cells.
How does transforming growth factor β (TGF-β) interact with proteoglycans?
Stimulates synthesis and secretion of proteoglycans in certain cells.
Which proteoglycan core proteins have growth factor–like domains?
versican and lymphocyte homing receptor.
What might these growth factor–like domains do?
Possibly interact with cell membrane growth factor receptors (mechanism not fully understood).
What role do proteoglycans play in the human knee joint?
They allow the joint to absorb shock during movement.
How does articular cartilage move against the meniscus?
With extremely low friction.