A unique combination of glycoside hydrolases in Streptococcus suis specifically and sequentially acts on host-derived αGal-epitope glycans
| Autor: | Gang Li, Jinlu Zhu, Dong Wei, Mengmeng Huang, Ran Liu, Fang Xie, Francis J. Castellino, Guanghui Dang, Ping Chen, Yueling Zhang, Siguo Liu, Ziyin Cui |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Glycan 030102 biochemistry & molecular biology biology Host–pathogen interaction Streptococcus suis Cell Biology biology.organism_classification Biochemistry Epitope 03 medical and health sciences 030104 developmental biology Enzyme chemistry biology.protein Glycoside hydrolase Enzyme kinetics Surface plasmon resonance Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 295:10638-10652 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra119.011977 |
| Popis: | Infections by many bacterial pathogens rely on their ability to degrade host glycans by producing glycoside hydrolases (GHs). Here, we discovered a conserved multifunctional GH, SsGalNagA, containing a unique combination of two family 32 carbohydrate-binding modules (CBM), a GH16 domain and a GH20 domain, in the zoonotic pathogen Streptococcus suis 05ZYH33. Enzymatic assays revealed that the SsCBM-GH16 domain displays endo-(β1,4)-galactosidase activity specifically toward the host-derived αGal epitope Gal(α1,3)Gal(β1,4)Glc(NAc)-R, whereas the SsGH20 domain has a wide spectrum of exo-β-N-acetylhexosaminidase activities, including exo-(β1,3)-N-acetylglucosaminidase activity, and employs this activity to act in tandem with SsCBM-GH16 on the αGal-epitope glycan. Further, we found that the CBM32 domain adjacent to the SsGH16 domain is indispensable for SsGH16 catalytic activity. Surface plasmon resonance experiments uncovered that both CBM32 domains specifically bind to αGal-epitope glycan, and together they had a KD of 3.5 mm toward a pentasaccharide αGal-epitope glycan. Cell-binding and αGal epitope removal assays revealed that SsGalNagA efficiently binds to both swine erythrocytes and tracheal epithelial cells and removes the αGal epitope from these cells, suggesting that SsGalNagA functions in nutrient acquisition or alters host signaling in S. suis. Both binding and removal activities were blocked by an αGal-epitope glycan. SsGalNagA is the first enzyme reported to sequentially act on a glycan containing the αGal epitope. These findings shed detailed light on the evolution of GHs and an important host-pathogen interaction. |
| Databáze: | OpenAIRE |
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