Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

PLoS Pathogens

Iain B. H. Wilson¹  Shi Yan¹  Martin A. Wälti²  Markus Künzler²  Silvia Bleuler-Martinez²  Pascal Egloff²  Markus Aebi²  Mario Schubert³  Frédéric H.-T. Allain³  Alex Butschi⁴  Michael O. Hengartner⁴  Katrin Stutz⁴ 

[1] Department of Chemistry, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria;Institute of Microbiology, ETH Zürich, Zürich, Switzerland;Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland;Institute of Molecular Life Sciences, University of Zürich, Switzerland

关键词: Lectins;    Carbohydrates;    Toxicity;    Caenorhabditis elegans;    Fungal structure;    NMR spectroscopy;    Protein structure;    Gastrointestinal tract;   

DOI  :  10.1371/journal.ppat.1002706

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies have been shown to play a role in the defence of multicellular fungi against predators and parasites. Here, we present a novel fruiting body lectin, CCL2, from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its NMR solution structure in complex with the trisaccharide, GlcNAcβ1,4[Fucα1,3]GlcNAc, to which it binds with high specificity and affinity in vitro. The structure reveals that the monomeric CCL2 adopts a β-trefoil fold and recognizes the trisaccharide by a single, topologically novel carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification of C. elegans mutants resistant to this lectin show that its nematotoxicity is mediated by binding to α1,3-fucosylated N-glycan core structures of nematode glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these target glycoproteins localize to the C. elegans intestine. Since the identified glycoepitope is characteristic for invertebrates but absent from fungi, our data show that the defence function of fruiting body lectins is based on the specific recognition of non-self carbohydrate structures. The trisaccharide specifically recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom allergens implying this particular glycoepitope is targeted by both fungal defence and mammalian immune systems. In summary, our results demonstrate how the plasticity of a common protein fold can contribute to the recognition and control of antagonists by an innate defence mechanism, whereby the monovalency of the lectin for its ligand implies a novel mechanism of lectin-mediated toxicity.

【 授权许可】

CC BY