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

Liz Adams, Peter Rice, Bridget Graves, Harry E Ensley, Hai Yu, Gordon D Brown, Siamon Gordon, Mario A Monteiro, Erzsebet Papp-Szabo, Douglas W Lowman, Trevor D Power, Michael F Wempe, David L Williams

Research output: Contribution to journalArticle

158 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume325
Issue number1
Early online date2 Jan 2008
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Glucans
Polymers
beta-Glucans
epiglucan
dectin 1
Ligands
Biological Products
Innate Immunity
C-Type Lectins
Pattern Recognition Receptors
Biopolymers
Candida albicans

Keywords

  • Animals
  • Carbohydrate Conformation
  • Cell Line
  • Humans
  • Immunity, Innate
  • Ligands
  • Membrane Proteins
  • Mice
  • Mitosporic Fungi
  • Nerve Tissue Proteins
  • Protein Binding
  • Substrate Specificity
  • Transfection
  • Yeasts
  • beta-Glucans

Cite this

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. / Adams, Liz; Rice, Peter; 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; Williams, David L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 325, No. 1, 04.2008, p. 115-123.

Research output: Contribution to journalArticle

Adams, L, Rice, P, Graves, B, Ensley, HE, Yu, H, Brown, GD, Gordon, S, Monteiro, MA, Papp-Szabo, E, Lowman, DW, Power, TD, Wempe, MF & Williams, DL 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, no. 1, pp. 115-123. https://doi.org/10.1124/jpet.107.133124
Adams, Liz ; Rice, Peter ; 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 ; Williams, David L. / 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. In: Journal of Pharmacology and Experimental Therapeutics. 2008 ; Vol. 325, No. 1. pp. 115-123.
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AU - Adams, Liz

AU - Rice, Peter

AU - Graves, Bridget

AU - Ensley, Harry E

AU - Yu, Hai

AU - Brown, Gordon D

AU - Gordon, Siamon

AU - Monteiro, Mario A

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KW - Membrane Proteins

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KW - Mitosporic Fungi

KW - Nerve Tissue Proteins

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KW - Substrate Specificity

KW - Transfection

KW - Yeasts

KW - beta-Glucans

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