Structure of the Fungal Beta-Glucan-Binding Immune Receptor Dectin-1: Implications for Function.
James Brown,Christopher A. O’Callaghan,Andrew S J Marshall,Robert J.C. Gilbert,Christian Siebold,Siamon Gordon,Gordon D. Brown,E Y Jones +7 more
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TLDR
Several dectin‐1 crystal structures are reported, including a high‐resolution structure and a 2.8 Å resolution structure in which a short soaked natural β‐glucan is trapped in the crystal lattice, which suggest potential mechanisms of defense against fungal pathogens.Abstract:
The murine molecule dectin-1 (known as the β-glucan receptor in humans) is an immune cell surface receptor implicated in the immunological defense against fungal pathogens. Sequence analysis has indicated that the dectin-1 extracellular domain is a C-type lectin-like domain, and functional studies have established that it binds fungal β-glucans. We report several dectin-1 crystal structures, including a high-resolution structure and a 2.8 A resolution structure in which a short soaked natural β-glucan is trapped in the crystal lattice. In vitro characterization of dectin-1 in the presence of its natural ligand indicates higher-order complex formation between dectin-1 and β-glucans. These combined structural and biophysical data considerably extend the current knowledge of dectin-1 structure and function, and suggest potential mechanisms of defense against fungal pathogens.read more
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Computational and Experimental Prediction of Human C-Type Lectin Receptor Druggability
TL;DR: The data indicate that small molecule ligands for a larger panel of CTLRs can be developed, and highlight limitations of current in silico approaches to druggability assessment, with regard to carbohydrate-binding proteins.
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Immunocompetent molecules and their response network in horseshoe crabs.
TL;DR: Horseshoe crab hemocyte selectively responds to bacterial lipopolysaccharides, which depends critically on the proteolytic activity of the LPS-responsive serine protease zymogen factor C, and coordinately effects pathogen recognition and killing, prophenoloxidase activation, complement activation and TGase-dependent wound healing.
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Molecular Recognition in C-Type Lectins: The Cases of DC-SIGN, Langerin, MGL, and L-Sectin.
Pablo Valverde,J. Daniel Martínez,F. Javier Cañada,Ana Ardá,Jesús Jiménez-Barbero,Jesús Jiménez-Barbero +5 more
TL;DR: The current knowledge about four key C‐type lectins whose importance has been steadily growing in recent years are summarized, focusing in particular on how glycan recognition takes place at the molecular level, but also looking at recent progresses in the quest for therapeutics.
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Anti-hepatoma activity of the stiff branched β-D-glucan and effects of molecular weight
TL;DR: The AF1 β-glucan was a potent natural drug candidate with high anti-cancer activities and less cytotoxicity, and the AF1 sample with a moderate molecular weight existed in aqueous solution as a more extended chain conformation, which plays an important role in activating immune responses.
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The role of dectin-1 in health and disease.
TL;DR: In this article, the impact of Dectin-1 polymorphisms in modulating protein expression and generation of non-optimal immune responses through defective collaborations is highlighted, further underlining their therapeutic potential.
References
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