Nature Structural & Molecular Biology11, 591 - 598 (2004)
Published online: 13 June 2004; | doi:10.1038/nsmb784
Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR
Yuan Guo1, 5, Hadar Feinberg2, 5, Edward Conroy1, Daniel A Mitchell1, Richard Alvarez3, Ola Blixt4, Maureen E Taylor1, William I Weis2
& Kurt Drickamer1
1
Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
2
Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
3
Department of Biochemistry & Molecular Biology, Protein-Carbohydrate Interaction Core H, Consortium for Functional Glycomics, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
4
Department of Molecular Biology, Consortium for Functional Glycomics, Carbohydrate Synthesis and Protein Expression Core D, CB248, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Both the dendritic cell receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR bind human immunodeficiency virus and enhance infection. However, biochemical and structural comparison of these receptors now reveals that they have very different physiological functions. By screening an extensive glycan array, we demonstrated that DC-SIGN and DC-SIGNR have distinct ligand-binding properties. Our structural and mutagenesis data explain how both receptors bind high-mannose oligosaccharides on enveloped viruses and why only DC-SIGN binds blood group antigens, including those present on microorganisms. DC-SIGN mediates endocytosis, trafficking as a recycling receptor and releasing ligand at endosomal pH, whereas DC-SIGNR does not release ligand at low pH or mediate endocytosis. Thus, whereas DC-SIGN has dual ligand-binding properties and functions both in adhesion and in endocytosis of pathogens, DC-SIGNR binds a restricted set of ligands and has only the properties of an adhesion receptor.
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