QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jpet.107.133124v1 325/1/115    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adams, E. L. Articles by Williams, D. L. Search for Related Content PubMed PubMed Citation Articles by Adams, E. L. Articles by Williams, D. L.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

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

Departments of Surgery (E.L.A., B.G., H.E.E., D.W.L., D.L.W.) and Pharmacology (P.J.R., M.F.W.), James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee; Delaware Biotechnology Institute, University of Delaware, Newark, Delaware (E.L.A.); Department of Chemistry, Tulane University, New Orleans, Louisiana (H.E.E., H.Y.); Institute of Infectious Disease and Molecular Medicine (G.D.B.), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom (S.G.); Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, Canada (M.A.M., E.P.-S.); Global Analytical Services, Eastman Chemical Company, Kingsport, Tennessee (D.W.L.); and Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas (T.D.P.)

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 (13)-β/(16)-β-glucans as well as nonglucan polymers. Dectin-1 is highly specific for glucans with a pure (13)-β-linked backbone structure. Although Dectin-1 is highly specific for (13)-β-D-glucans, it does not recognize all glucans equally. Dectin-1 differentially interacted with (13)-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 (16)-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.

This article has been cited by other articles:

				J. Vera, R. Fenutria, O. Canadas, M. Figueras, R. Mota, M.-R. Sarrias, D. L. Williams, C. Casals, J. Yelamos, and F. Lozano From the Cover: The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome PNAS, February 3, 2009; 106(5): 1506 - 1511. [Abstract] [Full Text] [PDF]