#TRACK CONCATENATOR J ACTIVATOR#

#TRACK CONCATENATOR J ACTIVATOR#

Combining the function of activator and repressor, GAG chains can favour a certain ligand/receptor complex, acting as a selector. GAG chains that block the ligand-binding site on a receptor act as a repressor. GAG chains act as an activator when the formation of a ligand/receptor complex is facilitated. Ligand-induced receptor pairing leads to a signal across the cell membrane that can trigger cytoskeleton reorganization and a transcriptional response. Schematic of GAG polysaccharides (as strings attached to proteoglycans embedded in the membrane, in red) regulating the formation of ligand/receptor complexes. GAGs as extracellular switches in ligand/receptor complex formation. The GAG polymer acts as a concatenator, bringing multiple receptor/ligand complexes together on the cell surface ( figure 1).įigure 1. There is yet another scenario, where long-chain GAG polymers can string together multiple proteins with positively charged patches. In addition, combining the roles described above for repressor and activator, binding of the GAG polymer might favour formation of one complex over another, in which case it acts as a selector. The GAG polymer acts as a repressor, inhibiting formation of this specific complex. In this case, the GAG polymer binds to the partner that has a positively charged patch, and it may prevent binding of the partner with a negatively charged patch. There are also receptor/ligand complexes that bind through surfaces that have complementary charges. On the cell surface, the GAG polymer can act as an activator that helps to assemble a receptor/ligand complex ( figure 1). When a GAG polymer binds to the positive patch, it neutralizes the protein surface and may facilitate or enhance binding of a protein partner. GAG molecules are very acidic, and they bind proteins on positive patches often delineated by clusters of arginines and lysines that surround the sugar-associated sulfate groups. Many extracellular matrix proteins and receptors bind GAGs, and they are also involved in forming protein–protein complexes. Glycosaminoglycans (GAGs) are a class of long unbranched polymers of amino and uronic sugars. We believe that it is worthwhile to study the role of GAGs as molecular switches, as this may lead to novel drug candidates to target processes such as angiogenesis, neuroregeneration and tumour metastasis. Based on these principles, we propose that individual GAG polymers may affect several receptor pathways in parallel, orchestrating a cellular response to an environmental cue. We categorize several switches that lead to ligand activation, inhibition, selection and addition, based on recent structural studies of select receptor/ligand complexes. Here, we focus on the role of GAG polymers in mediating interactions between cell surface receptors and their ligands. Despite the biochemical and structural characterization of individual protein/GAG interactions, there is no concept available that links the molecular mechanisms of GAG/protein engagements to tissue development. Glycosaminoglycans (GAGs) play a widespread role in embryonic development, as deletion of enzymes that contribute to GAG synthesis lead to deficiencies in cell migration and tissue modelling.

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