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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides
DOI:
10.1038/s41467-020-14754-7
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

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