Glycan-binding protein (GBP) Ligands (Glycans which are bound by GBPs):

The natural ligands for GBPs can be quite elusive. For example, it took almost 10 years from the detection of P-selectin’s glycan binding properties to reach the definitive conclusion that a certain specific postranslationally modified form of the polypeptide PSGL-1 was the functionally relevant natural ligand for this GBP. There are many reasons for such difficulties, including the fact that glycan binding is often of relatively low affinity and relies on multivalency to achieve adequate avidity. It has been said that investigators continue to incorrectly state that “PSGL-1 is the ligand for P-selectin,” without realizing that while the PSGL-1 polypeptide backbone is expressed in many cell types, it is only the correctly sialylated, fucosylated,a nd tyrosine-sulfated form found in certain cells that can function as a P-selectin ligand. In this respect, it has been suggested to define the ligand as the glycan(s) bound by the GBP, the protein or lipid to which the glycan(s) are bound as the “carrier” and the composite of the glycan and the carrier as the “counter-receptor”.