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Journal Articles Nature Communications Year : 2021

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

Rebecca Nason
  • Function : Author
Christian Büll
  • Function : Author
Andriana Konstantinidi
  • Function : Author
Lingbo Sun
  • Function : Author
Zilu Ye
  • Function : Author
Adnan Halim
  • Function : Author
Wenjuan Du
  • Function : Author
Daniel Sørensen
Fabien Durbesson
  • Function : Author
Sanae Furukawa
  • Function : Author
Ulla Mandel
Hiren Joshi
Leo Alexander Dworkin
Lars Hansen
  • Function : Author
Leonor David
Tina Iverson
Barbara Bensing
  • Function : Author
Paul Sullam
  • Function : Author
Ajit Varki
  • Function : Author
Erik De Vries
  • Function : Author
Cornelis de Haan
Renaud Vincentelli
Bernard Henrissat
Sergey Vakhrushev
Henrik Clausen

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.

Dates and versions

hal-03524039 , version 1 (13-01-2022)

Identifiers

Cite

Rebecca Nason, Christian Büll, Andriana Konstantinidi, Lingbo Sun, Zilu Ye, et al.. Display of the human mucinome with defined O-glycans by gene engineered cells. Nature Communications, 2021, 12 (1), pp.4070. ⟨10.1038/s41467-021-24366-4⟩. ⟨hal-03524039⟩
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