Differential High-Affinity Interaction of Dectin-1 With Natural or Synthetic Glucans Is Dependent Upon Primary Structure and Is Influenced by Polymer Chain Length and Side-Chain Branching
Document Type
Article
Publication Date
4-1-2008
Description
Glucans are structurally diverse fungal biopolymers that stimulate innate immunity and are fungal pathogen-associated molecular patterns. Dectin-1 is a C-type lectin-like pattern recognition receptor that binds glucans and induces innate immune responses to fungal pathogens. We examined the effect of glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1→3)-β/(1→6)-β- glucans as well as nonglucan polymers. Dectin-1 is highly specific for glucans with a pure (1→3)-β-linked backbone structure. Although Dectin-1 is highly specific for (1→3)-β-D-glucans, it does not recognize all glucans equally. Dectin-1 differentially interacted with (1→3)-β-D- glucans over a very wide range of binding affinities (2.6 mM-2.2 pM). One of the most striking observations that emerged from this study was the remarkable high-affinity interaction of Dectin-1 with certain glucans (2.2 pM). These data also demonstrated that synthetic glucan ligands interact with Dectin-1 and that binding affinity increased in synthetic glucans containing a single glucose side-chain branch. We also observed differential recognition of glucans derived from saprophytes and pathogens. We found that glucan derived from a saprophytic yeast was recognized with higher affinity than glucan derived from the pathogen Candida albicans. Structural analysis demonstrated that glucan backbone chain length and (1→6)-β side-chain branching strongly influenced Dectin-1 binding affinity. These data demonstrate: 1) the specificity of Dectin-1 for glucans; 2) that Dectin-1 differentiates between glucan ligands based on structural determinants; and 3) that Dectin-1 can recognize and interact with both natural product and synthetic glucan ligands.
Citation Information
Adams, Elizabeth; Rice, Peter J.; Graves, Bridget; Ensley, Harry E.; Yu, Hai; Brown, Gordon D.; Gordon, Siamon; Monteiro, Mario A.; Papp-Szabo, Erzsebet; Lowman, Douglas W.; Power, Trevor D.; Wempe, Michael F.; and Williams, David L.. 2008. Differential High-Affinity Interaction of Dectin-1 With Natural or Synthetic Glucans Is Dependent Upon Primary Structure and Is Influenced by Polymer Chain Length and Side-Chain Branching. Journal of Pharmacology and Experimental Therapeutics. Vol.325(1). 115-123. https://doi.org/10.1124/jpet.107.133124 PMID: 18171906 ISSN: 0022-3565