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

Author

Listed:
  • Beatriz Trastoy

    (Bizkaia Technology Park)

  • Jonathan J. Du

    (University of Maryland School of Medicine
    Emory University School of Medicine)

  • Erik H. Klontz

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Chao Li

    (University of Maryland)

  • Javier O. Cifuente

    (Bizkaia Technology Park)

  • Lai-Xi Wang

    (University of Maryland)

  • Eric J. Sundberg

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine
    Emory University School of Medicine)

  • Marcelo E. Guerin

    (Bizkaia Technology Park
    IKERBASQUE, Basque Foundation for Science)

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.

Suggested Citation

  • Beatriz Trastoy & Jonathan J. Du & Erik H. Klontz & Chao Li & Javier O. Cifuente & Lai-Xi Wang & Eric J. Sundberg & Marcelo E. Guerin, 2020. "Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14754-7
    DOI: 10.1038/s41467-020-14754-7
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    Cited by:

    1. Carla Pérez-Cruz & Alicia Moraleda-Montoya & Raquel Liébana & Oihana Terrones & Uxue Arrizabalaga & Mikel García-Alija & Maier Lorizate & Ana Martínez Gascueña & Isabel García-Álvarez & Jon Ander Niet, 2024. "Mechanisms of recalcitrant fucoidan breakdown in marine Planctomycetota," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Beatriz Trastoy & Jonathan J. Du & Javier O. Cifuente & Lorena Rudolph & Mikel García-Alija & Erik H. Klontz & Daniel Deredge & Nazneen Sultana & Chau G. Huynh & Maria W. Flowers & Chao Li & Diego E. , 2023. "Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Mikel García-Alija & Jonathan J. Du & Izaskun Ordóñez & Asier Diz-Vallenilla & Alicia Moraleda-Montoya & Nazneen Sultana & Chau G. Huynh & Chao Li & Thomas Connor Donahue & Lai-Xi Wang & Beatriz Trast, 2022. "Mechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Ann-Sophie Rüttiger & Daniel Ryan & Luisella Spiga & Vanessa Lamm-Schmidt & Gianluca Prezza & Sarah Reichardt & Madison Langford & Lars Barquist & Franziska Faber & Wenhan Zhu & Alexander J. Westerman, 2025. "The global RNA-binding protein RbpB is a regulator of polysaccharide utilization in Bacteroides thetaiotaomicron," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    5. Diego E. Sastre & Nazneen Sultana & Marcos V. A. S. Navarro & Maros Huliciak & Jonathan Du & Javier O. Cifuente & Maria Flowers & Xu Liu & Pete Lollar & Beatriz Trastoy & Marcelo E. Guerin & Eric J. S, 2024. "Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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