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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides

DOI: 10.1038/s41467-020-14754-7 DOI Help

Authors: Beatriz Trastoy (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Jonathan J. Du (University of Maryland School of Medicine) , Erik H. Klontz (University of Maryland School of Medicine) , Chao Li (University of Maryland) , Javier O. Cifuente (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Lai-xi Wang (University of Maryland) , Eric J. Sundberg (Emory University School of Medicine; University of Maryland School of Medicine) , Marcelo E. Guerin (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); IKERBASQUE, Basque Foundation for Science)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: February 2020
Diamond Proposal Number(s): 20113

Open Access Open Access

Abstract: 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.

Journal Keywords: Glycobiology

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: BL13-XALOC at ALBA

Documents:
s41467-020-14754-7.pdf