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 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.
Menon
Sindhu
S
Department of Chemistry and Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Rosenberg
Kenneth
K
Graham
Sarah A
SA
Ward
Eliot M
EM
Taylor
Maureen E
ME
Drickamer
Kurt
K
Leckband
Deborah E
DE
D000268:Adhesiveness; D001665:Binding Sites / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008051:Lipid Bilayers; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin