Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function.
The murine molecule dectin-1 (known as the beta-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 beta-glucans. We report several dectin-1 crystal structures, including a high-resolution structure and a 2.8 angstroms resolution structure in which a short soaked natural beta-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 beta-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.
Brown
James
J
CR-UK Receptor Structure Research Group, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
O'Callaghan
Chris A
CA
Marshall
Andrew S J
AS
Gilbert
Robert J C
RJ
Siebold
Christian
C
Gordon
Siamon
S
Brown
Gordon D
GD
Jones
E Yvonne
EY
D000818:Animals; D002413:Cations, Divalent; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D005936:Glucans; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D047071:beta-Glucans / Q000737:chemistry / Q000378:metabolism; D000099181:Dectin-1
D002413:Cations, Divalent; D005656:Fungal Proteins; D005936:Glucans; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011971:Receptors, Immunologic; D047071:beta-Glucans; D000099181:Dectin-1; C045268:beta-glucan receptor; C008247:laminaran