Title

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.

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