Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
Date
2020Journal
Nature communicationsPublisher
Springer NatureType
Article
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The human gut microbiota plays a central role not only in regulating the metabolism of nutrients but also promoting immune homeostasis, immune responses and protection against pathogen colonization. The genome of the Gram-negative symbiont Bacteroides thetaiotaomicron, a dominant member of the human intestinal microbiota, encodes polysaccharide utilization loci PULs, the apparatus required to orchestrate the degradation of a specific glycan. EndoBT-3987 is a key endo-β-N-acetylglucosaminidase (ENGase) that initiates the degradation/processing of mammalian high-mannose-type (HM-type) N-glycans in the intestine. Here, we provide structural snapshots of EndoBT-3987, including the unliganded form, the EndoBT-3987-Man9GlcNAc2Asn substrate complex, and two EndoBT-3987-Man9GlcNAc and EndoBT-3987-Man5GlcNAc product complexes. In combination with alanine scanning mutagenesis and activity measurements we unveil the molecular mechanism of HM-type recognition and specificity for EndoBT-3987 and an important group of the GH18 ENGases, including EndoH, an enzyme extensively used in biotechnology, and for which the mechanism of substrate recognition was largely unknown.Keyword
glycansGlycomics
Crystallography, X-Ray
Polysaccharides
Gastrointestinal Microbiome
Bacteroides thetaiotaomicron
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079361800&doi=10.1038%2fs41467-020-14754-7&partnerID=40&md5=1281952b8bd63f553e65eb0ca2a86f7d; http://hdl.handle.net/10713/12127ae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-14754-7
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