Title :
Sialylated O-glycans and sulfated
tyrosines in the NH2-terminal
domain of
CC chemokine receptor 5 contribute to high affinity binding of chemokines
Abstract :
- The chemokine receptor CCR5 plays an important role in leukocyte chemotaxis and activation, and also acts as a coreceptor for human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV)
- We provide evidence that CCR5 is O-glycosylated on serine 6 in the NH2 terminus
- The O-linked glycans , particularly sialic acid moieties, significantly contribute to binding of the chemokine ligands
- By contrast, removal of O-linked oligosaccharide exerted little effect on HIV-1 infection
- Sulfation of specific tyrosine residues in the CCR5 NH2 terminus was important for efficient beta-chemokine binding
- Thus, as has been observed for the binding of selectins and their ligands, O-linked carbohydrates and tyrosine sulfates play major roles in promoting the interaction of chemokines with CCR5
- The resulting flexible arrays of negative charges on the CCR5 surface may allow specific, high-affinity interactions with diverse chemokine ligands
- Although this is the first example of O-linked oligosaccharides and tyrosine sulfates playing a role in chemokine binding, the high density of serines, threonines and tyrosines in the N-termini of many CC chemokine receptors suggests that these posttranslational modifications may commonly contribute to chemokine binding