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.
abstract: 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)-beta/(1-->6)-beta-glucans as well as nonglucan polymers. Dectin-1 is highly specific for glucans with a pure (1-->3)-beta-linked backbone structure. Although Dectin-1 is highly specific for (1-->3)-beta-d-glucans, it does not recognize all glucans equally. Dectin-1 differentially interacted with (1-->3)-beta-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)-beta 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.
authors.affiliation: Department of Surgery, PO Box 70575, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Adams
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rice
authors.forename: Bridget
authors.initials: B
authors.lastname: Graves
authors.forename: Harry E
authors.initials: HE
authors.lastname: Ensley
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Mario A
authors.initials: MA
authors.lastname: Monteiro
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Papp-Szabo
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Lowman
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Power
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wempe
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D003904:Mitosporic Fungi / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D014162:Transfection; D015003:Yeasts / Q000737:chemistry; D047071:beta-Glucans / Q000737:chemistry* / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047071:beta-Glucans; D000099181:Dectin-1