Caenorhabditis elegans N-glycan core beta-galactoside confers sensitivity towards nematotoxic fungal galectin CGL2.
The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a Galbeta1,4Fucalpha1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the Galbeta1,4Fucalpha1,6GlcNAc trisaccharide at 1.5 A resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms.
Butschi
Alex
A
Institute of Molecular Biology, University of Zürich, Zürich, Switzerland.
Titz
Alexander
A
Wälti
Martin A
MA
Olieric
Vincent
V
Paschinger
Katharina
K
Nöbauer
Katharina
K
Guo
Xiaoqiang
X
Seeberger
Peter H
PH
Wilson
Iain B H
IB
Aebi
Markus
M
Hengartner
Michael O
MO
Künzler
Markus
M
D000363:Agaricales / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005697:Galactosides / Q000378:metabolism*; D037501:Galectin 2 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009349:Nematode Infections / Q000276:immunology* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
C103751:CGL2 protein, Coprinus cinereus; D029742:Caenorhabditis elegans Proteins; D005656:Fungal Proteins; D005697:Galactosides; D037501:Galectin 2; C007816:beta-galactoside