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How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

DOI: 10.1073/pnas.1704367114 DOI Help

Authors: Alan Cartmell (Institute for Cell and Molecular Biosciences, Newcastle University) , Elisabeth C. Lowe (Institute for Cell and Molecular Biosciences, Newcastle University) , Arnaud Basle (Institute for Cell and Molecular Biosciences, Newcastle University) , Susan J. Firbank (Institute for Cell and Molecular Biosciences, Newcastle University) , Didier A. Ndeh (Institute for Cell and Molecular Biosciences, Newcastle University) , Heath Murray (Institute for Cell and Molecular Biosciences, Newcastle University) , Nicolas Terrapon (CNRS, Aix-Marseille University) , Vincent Lombard (CNRS, Aix-Marseille University) , Bernard Henrissat (CNRS, Aix-Marseille University; Institut National de la Recherche Agronomique; King Abdulaziz University) , Jeremy E. Turnbull (Institute of Integrative Biology, University of Liverpool) , Mirjam Czjzek (Université Pierre-et-Marie-Curie) , Harry J. Gilbert (Institute for Cell and Molecular Biosciences, Newcastle University) , David N. Bolam (Institute for Cell and Molecular Biosciences, Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 114 , PAGES 7037 - 7042

State: Published (Approved)
Published: July 2017
Diamond Proposal Number(s): 311 , 9948

Abstract: The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides, indicating that the model developed is of generic relevance to this important microbial community.

Journal Keywords: human gut microbiota; glycosaminoglycan degradation; heparin; heparan sulfate; Bacteroides thetaiotaomicron

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 22/09/2017 09:43

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