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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β‐glucan recognition by the innate immune system
TL;DR: This review explores what is currently known about β‐glucan recognition and how this recognition stimulates immune responses, and special emphasis is placed on Dectin‐1, as the authors know the most about how this key β‐ glucan receptor translates recognition into intracellular signaling, stimulates cellular responses,and participates in orchestrating the adaptive immune response.
Journal ArticleDOI
The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans
Christine A. Wells,Judith Salvage-Jones,Xin Li,Kelly J Hitchens,Suzanne Butcher,Rachael Z. Murray,Anthony G Beckhouse,Yu-Lan-Sandra Lo,Silvia Manzanero,Christian Cobbold,Kate Schroder,Bo Ma,Sally Orr,Lauren Stewart,Daniel Lebus,Peter Sobieszczuk,David A. Hume,Jennifer L. Stow,Helen Blanchard,Robert B. Ashman +19 more
TL;DR: Mincle, a C-type lectin, is expressed predominantly on macrophages, and is here shown to play a role in macrophage responses to the yeast Candida albicans.
The Macrophage Inducible c-type lectin, Mincle, is an essential component of the innate-immune response to Candida albicans
Christine A. Wells,Judith Salvage-Jones,Xin Li,Kelly J Hitchens,Suzanne Butcher,Rachael Z. Murray,Anthony G Beckhouse,Yu-Lan-Sandra Lo,Silvia Manzanero,Christian Cobbold,Kate Schroder,Bo Ma,Sally Orr,Lauren Stewart,Daniel Lebus,Peter Sobieszczuk,David A. Hume,Jennifer L. Stow,Helen Blanchard,Robert B. Ashman +19 more
TL;DR: In this paper, the c-type lectin Mincle was observed to localise in the phagocytic cup of macrophages in response to a range of stimuli.
Journal ArticleDOI
Tasting the fungal cell wall.
TL;DR: A comprehensive understanding of the interactions between the host membrane receptors and the fungal cell wall components is still lacking and thefungal adhesins playing a role in adhesion to host have been only explored in yeasts.
Journal ArticleDOI
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.
Elizabeth L. Adams,Peter J. Rice,Bridget M. 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 +12 more
TL;DR: This study 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)-β/(1→6)-β-glucans as well as nonglucan polymers and found that glucan derived from a saprophytic yeast was recognized with higher affinity than glucanderived from the pathogen Candida albicans.
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