Two complementary α-fucosidases from Streptococcus pneumonia promote complete degradation of host-derived carbohydrate antigens
| dc.contributor.author | Hobbs, Joanne K. | |
| dc.contributor.author | Pluvinage, Benjamin | |
| dc.contributor.author | Robb, Melissa | |
| dc.contributor.author | Smith, Steven P. | |
| dc.contributor.author | Boraston, Alisdair B. | |
| dc.date.accessioned | 2021-01-28T23:34:20Z | |
| dc.date.available | 2021-01-28T23:34:20Z | |
| dc.date.copyright | 2019 | en_US |
| dc.date.issued | 2019 | |
| dc.description.abstract | An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae. Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown. Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively. X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif. Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion. In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes. These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this. Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae–host interaction. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | We thank the beamline staff at the Stanford Synchrotron Research Laboratory (SSRL). SSRL is a Directorate of Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory and an Office of Science User Facility operated for the United States Department of Energy (DOE) Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program (Grant P41RR001209), and the National Institute of General Medical Sciences. Research described in this paper was performed using beamline 08B1-1 at the Canadian Light Source, which is supported by the Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada, the University of Saskatchewan, the Government of Saskatchewan, Western Economic Diversification Canada, the National Research Council Canada, and the Canadian Institutes of Health Research. | en_US |
| dc.identifier.citation | Hobbs, J. K., Pluvinage, B., Robb, M., Smith, S. P., & Boraston, A. B. (2019). Two complementary α-fucosidases from Streptococcus pneumonia promote complete degradation of host-derived carbohydrate antigens. Journal of Biological Chemistry, 294(34), 12670-12682. https://doi.org/10.1074/jbc.RA119.009368. | en_US |
| dc.identifier.uri | https://doi.org/10.1074/jbc.RA119.009368 | |
| dc.identifier.uri | http://hdl.handle.net/1828/12614 | |
| dc.language.iso | en | en_US |
| dc.publisher | Journal of Biological Chemistry | en_US |
| dc.subject | Streptococcus | |
| dc.subject | glycoside hydrolase | |
| dc.subject | host-pathogen interaction | |
| dc.subject | structure-function | |
| dc.subject | X-ray crystallography | |
| dc.subject.department | Department of Biochemistry and Microbiology | |
| dc.title | Two complementary α-fucosidases from Streptococcus pneumonia promote complete degradation of host-derived carbohydrate antigens | en_US |
| dc.type | Article | en_US |