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.
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.
Adams
Elizabeth L
EL
Department of Surgery, PO Box 70575, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Rice
Peter J
PJ
Graves
Bridget
B
Ensley
Harry E
HE
Yu
Hai
H
Brown
Gordon D
GD
Gordon
Siamon
S
Monteiro
Mario A
MA
Papp-Szabo
Erzsebet
E
Lowman
Douglas W
DW
Power
Trevor D
TD
Wempe
Michael F
MF
Williams
David L
DL
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
D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047071:beta-Glucans; D000099181:Dectin-1