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N-glycan Utilization by Bifidobacterium Gut Symbionts Involves a Specialist β-Mannosidase

Cordeiro, Rosa Lorizolla, Pirolla, Renan Augusto Siqueira, Persinoti, Gabriela Felix, Gozzo, Fábio Cesar, de Giuseppe, Priscila Oliveira, Murakami, Mario Tyago
Journal of molecular biology 2019 v.431 no.4 pp. 732-747
Bacteroidetes, Bifidobacterium, active sites, bees, beta-mannosidase, carbohydrates, depolymerization, digestive system, ecosystems, hosts, humans, intestinal microorganisms, moieties, nutrition, probiotics, rabbits, swine, symbionts, tryptophan
Bifidobacteria represent one of the first colonizers of human gut microbiota, providing to this ecosystem better health and nutrition. To maintain a mutualistic relationship, they have enzymes to degrade and use complex carbohydrates non-digestible by their hosts. To succeed in the densely populated gut environment, they evolved molecular strategies that remain poorly understood. Herein, we report a novel mechanism found in probiotic Bifidobacteria for the depolymerization of the ubiquitous 2-acetamido-2-deoxy-4-O-(β-d-mannopyranosyl)-d-glucopyranose (Man-β-1,4-GlcNAc), a disaccharide that composes the universal core of eukaryotic N-glycans. In contrast to Bacteroidetes, these Bifidobacteria have a specialist and strain-specific β-mannosidase that contains three distinctive structural elements conferring high selectivity for Man-β-1,4-GlcNAc: a lid that undergoes conformational changes upon substrate binding, a tryptophan residue swapped between the two dimeric subunits to accommodate the GlcNAc moiety, and a Rossmann fold subdomain strategically located near to the active site pocket. These key structural elements for Man-β-1,4-GlcNAc specificity are highly conserved in Bifidobacterium species adapted to the gut of a wide range of social animals, including bee, pig, rabbit, and human. Together, our findings uncover an unprecedented molecular strategy employed by Bifidobacteria to selectively uptake carbohydrates from N-glycans in social hosts.