2LIQ

Solution structure of CCL2 in complex with glycan

2LIQ の概要

• エントリーDOI: 10.2210/pdb2liq/pdb
• 関連するPDBエントリー: 2LIE
• NMR情報: BMRB: 17902
• 分子名称: CCL2 lectin, alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]methyl 2-acetamido-2-deoxy-beta-D-glucopyranoside (2 entities in total)
• 機能のキーワード: carbohydrate recognition, sugar binding protein
• 由来する生物種: Coprinopsis cinerea (Inky cap fungus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17188.85

構造登録者

Schubert, M.,Bleuler-Martinez, S.,Walti, M.A.,Egloff, P.,Aebi, M.,Kuenzler, M.,Allain, F.H.-T. (登録日: 2011-08-30, 公開日: 2012-06-06, 最終更新日: 2024-05-15)

主引用文献

Schubert, M.,Bleuler-Martinez, S.,Butschi, A.,Walti, M.A.,Egloff, P.,Stutz, K.,Yan, S.,Wilson, I.B.,Hengartner, M.O.,Aebi, M.,Allain, F.H.,Kunzler, M.
Plasticity of the beta-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System
Plos Pathog., 8:e1002706-e1002706, 2012

PubMed Abstract: 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.

PubMed: 22615566
DOI: 10.1371/journal.ppat.1002706

実験手法

SOLUTION NMR