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

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 Alexander Dworkin, Lars Hansen, Leonor David, Tina M. Iverson, Barbara A. Bensing, Paul M. Sullam, Ajit Varki, Erik de Vries, Cornelis A. M. Haan, Renaud Vincentelli, Bernard Henrissat, Sergey Y. Vakhrushev, Henrik Clausen () and Yoshiki Narimatsu ()
Additional contact information
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
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24366-4

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