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Display of the human mucinome with defined O-glycans by gene engineered cells

Author

Listed:
  • Rebecca Nason

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Christian Büll

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Andriana Konstantinidi

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Lingbo Sun

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Zilu Ye

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Adnan Halim

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Wenjuan Du

    (Section Virology, Division of Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University)

  • Daniel M. Sørensen

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Fabien Durbesson

    (Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université)

  • Sanae Furukawa

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Ulla Mandel

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Hiren J. Joshi

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Leo Alexander Dworkin

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Lars Hansen

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Leonor David

    (Institute of Molecular Pathology and Immunology of the University of Porto/I3S
    Medical Faculty of the University of Porto)

  • Tina M. Iverson

    (Departments of Pharmacology and Biochemistry, Vanderbilt University)

  • Barbara A. Bensing

    (Department of Medicine, The San Francisco Veterans Affairs Medical Center, and the University of California)

  • Paul M. Sullam

    (Department of Medicine, The San Francisco Veterans Affairs Medical Center, and the University of California)

  • Ajit Varki

    (The Glycobiology Research and Training Center, and the Department of Cellular and Molecular Medicine, University of California)

  • Erik de Vries

    (Section Virology, Division of Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University)

  • Cornelis A. M. Haan

    (Section Virology, Division of Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University)

  • Renaud Vincentelli

    (Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université)

  • Bernard Henrissat

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen
    Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille Université
    Department of Biological Sciences, King Abdulaziz University)

  • Sergey Y. Vakhrushev

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Henrik Clausen

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen)

  • Yoshiki Narimatsu

    (Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen
    GlycoDisplay ApS)

Abstract

Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids. Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins. Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells. Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.

Suggested Citation

  • Rebecca Nason & Christian Büll & Andriana Konstantinidi & Lingbo Sun & Zilu Ye & Adnan Halim & Wenjuan Du & Daniel M. Sørensen & Fabien Durbesson & Sanae Furukawa & Ulla Mandel & Hiren J. Joshi & Leo , 2021. "Display of the human mucinome with defined O-glycans by gene engineered cells," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24366-4
    DOI: 10.1038/s41467-021-24366-4
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    Cited by:

    1. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Janneke Elzinga & Yoshiki Narimatsu & Noortje Haan & Henrik Clausen & Willem M. Vos & Hanne L. P. Tytgat, 2024. "Binding of Akkermansia muciniphila to mucin is O-glycan specific," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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