Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 194, Issue 11, Pages 1661-1673Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.194.11.1661
Keywords
CCR5; O-glycosylation; sialic acid; tyrosine sulfation; HIV
Categories
Funding
- NIAID NIH HHS [AI28691, R01 AI043891, AI41851] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available