4USO

X-ray structure of the CCL2 lectin in complex with sialyl lewis X

4USO の概要

• エントリーDOI: 10.2210/pdb4uso/pdb
• 関連するPDBエントリー: 4USP 4UT5
• 関連するBIRD辞書のPRD_ID: PRD_900121
• 分子名称: CCL2 LECTIN, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: sugar binding protein, dimeric, fungal
• 由来する生物種: COPRINOPSIS CINEREA (INK CAP FUNGUS)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67237.87

構造登録者

Bleuler-Martinez, S.,Varrot, A.,Schubert, M.,Stutz, M.,Sieber, R.,Hengartner, M.,Aebi, M.,Kunzler, M. (登録日: 2014-07-11, 公開日: 2015-07-22, 最終更新日: 2024-01-10)

主引用文献

Bleuler-Martinez, S.,Stutz, K.,Sieber, R.,Collot, M.,Mallet, J.M.,Hengartner, M.,Schubert, M.,Varrot, A.,Kunzler, M.
Dimerization of the fungal defense lectin CCL2 is essential for its toxicity against nematodes.
Glycobiology, 27:486-500, 2017

PubMed Abstract: Lectins are used as defense effector proteins against predators, parasites and pathogens by animal, plant and fungal innate defense systems. These proteins bind to specific glycoepitopes on the cell surfaces and thereby interfere with the proper cellular functions of the various antagonists. The exact cellular toxicity mechanism is in many cases unclear. Lectin CCL2 of the mushroom Coprinopsis cinerea was previously shown to be toxic for Caenorhabditis elegans and Drosophila melanogaster. This toxicity is dependent on a single, high-affinity binding site for the trisaccharide GlcNAc(Fucα1,3)β1,4GlcNAc, which is a hallmark of nematode and insect N-glycan cores. The carbohydrate-binding site is located at an unusual position on the protein surface when compared to other β-trefoil lectins. Here, we show that CCL2 forms a compact dimer in solution and in crystals. Substitution of two amino acid residues at the dimer interface, R18A and F133A, interfered with dimerization of CCL2 and reduced toxicity but left carbohydrate-binding unaffected. These results, together with the positioning of the two carbohydrate-binding sites on the surface of the protein dimer, suggest that crosslinking of N-glycoproteins on the surface of intestinal cells of invertebrates is a crucial step in the mechanism of CCL2-mediated toxicity. Comparisons of the number and positioning of carbohydrate-binding sites among different dimerizing fungal β-trefoil lectins revealed a considerable variability in the carbohydrate-binding patterns of these proteins, which are likely to correlate with their respective functions.

PubMed: 27980000
DOI: 10.1093/glycob/cww113

実験手法

X-RAY DIFFRACTION (1.95 Å)