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

Sindhu Menon, Kenneth Rosenberg, Sarah A. Graham, Eliot M. Ward, Maureen E. Taylor, Kurt Drickamer, Deborah E. Leckband

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11524-11529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number28
DOIs
StatePublished - Jul 14 2009

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Binding Sites
Ligands
Polysaccharides
Carbohydrates
Lipid Bilayers
Oligosaccharides
Dendritic Cells
Cluster Analysis
HIV
Membranes
DC-specific ICAM-3 grabbing nonintegrin

Keywords

  • Adhesion
  • Molecular recognition
  • Multivalent receptors
  • Pathogen selectivity

ASJC Scopus subject areas

  • General

Cite this

Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements. / Menon, Sindhu; Rosenberg, Kenneth; Graham, Sarah A.; Ward, Eliot M.; Taylor, Maureen E.; Drickamer, Kurt; Leckband, Deborah E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 28, 14.07.2009, p. 11524-11529.

Research output: Contribution to journalArticle

Menon, Sindhu ; Rosenberg, Kenneth ; Graham, Sarah A. ; Ward, Eliot M. ; Taylor, Maureen E. ; Drickamer, Kurt ; Leckband, Deborah E. / Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 28. pp. 11524-11529.
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