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
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. O-glycans, , -, the NH2-terminal domain, domain
- 0. O-glycans, , CC chemokine receptor 5, O-glycans, -
- 2. O-glycosylated, , CCR5, -, serine 6
- 2. O-glycosylated, , CCR5, -, terminus
Output(Part-Of) (sent_index,
protein,
site):
- 0. CC chemokine receptor 5, domain
- 0. CC chemokine receptor 5, tyrosines
- 5. CCR5, terminus
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):