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
| ISSN: | 1521-0103 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cffaf3a293bb59cbadc80d177c46c48d https://pubmed.ncbi.nlm.nih.gov/18171906 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....cffaf3a293bb59cbadc80d177c46c48d |
| Autor: | Mario A. Monteiro, David L. Williams, Hai Yu, Siamon Gordon, Michael F. Wempe, Peter J. Rice, Erzsebet Papp-Szabo, Trevor D. Power, Douglas W. Lowman, Bridget M. Graves, Harry E. Ensley, Gordon D. Brown, Elizabeth L. Adams |
| Rok vydání: | 2008 |
| Předmět: |
beta-Glucans
Nerve Tissue Proteins macromolecular substances Plasma protein binding Biology Ligands Transfection Cell Line Substrate Specificity chemistry.chemical_compound Mice Yeasts Carbohydrate Conformation Animals Humans Lectins C-Type Glucan Pharmacology chemistry.chemical_classification Natural product Innate immune system Protein primary structure Pattern recognition receptor Membrane Proteins Yeast Immunity Innate carbohydrates (lipids) stomatognathic diseases chemistry Biochemistry Molecular Medicine Carbohydrate conformation Mitosporic Fungi Protein Binding |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 325(1) |
| ISSN: | 1521-0103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|