Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements

The dendritic cell receptor DC-SIGN mediates pathogen recognition by binding to glycans characteristic of pathogen surfaces, including those found on HIV. Clustering of carbohydrate-binding sites in the receptor tetramer is believed to be critical for targeting of pathogen glycans, but the arrangeme...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-07, Vol.106 (28), p.11524-11529
Main Authors: Menon, Sindhu, Rosenberg, Kenneth, Graham, Sarah A, Ward, Eliot M, Taylor, Maureen E, Drickamer, Kurt, Leckband, Deborah E
Format: Article
Language:English
Subjects:
Adhesion
Adhesiveness
Binding sites
Binding Sites - genetics
Biological Sciences
Carbohydrates
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Lectins, C-Type - genetics
Lectins, C-Type - metabolism
Ligands
Lipid bilayers
Lipid Bilayers - metabolism
Lipids
Membranes
Models, Molecular
Molecules
Oligosaccharides
Oligosaccharides - metabolism
Pathogens
Physical Sciences
Polysaccharides
Protein Binding
Protein Conformation
Receptors
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
T cell receptors
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Summary:The dendritic cell receptor DC-SIGN mediates pathogen recognition by binding to glycans characteristic of pathogen surfaces, including those found on HIV. Clustering of carbohydrate-binding sites in the receptor tetramer is believed to be critical for targeting of pathogen glycans, but the arrangement of these sites remains poorly understood. Surface force measurements between apposed lipid bilayers displaying the extracellular domain of DC-SIGN and a neoglycolipid bearing an oligosaccharide ligand provide evidence that the receptor is in an extended conformation and that glycan docking is associated with a conformational change that repositions the carbohydrate-recognition domains during ligand binding. The results further show that the lateral mobility of membrane-bound ligands enhances the engagement of multiple carbohydrate-recognition domains in the receptor oligomer with appropriately spaced ligands. These studies highlight differences between pathogen targeting by DC-SIGN and receptors in which binding sites at fixed spacing bind to simple molecular patterns.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0901783106