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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Rebecca Nason
  • Lingbo Sun
  • Wenjuan Du
  • Fabien Durbesson
  • Sanae Furukawa
  • Leo Alexander Dworkin
  • Leonor David
  • Tina M. Iverson
  • Barbara A. Bensing
  • Paul M. Sullam
  • Ajit Varki
  • Erik de Vries
  • Cornelis A.M. de Haan
  • Renaud Vincentelli
  • Bernard Henrissat

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.

OriginalsprogEngelsk
Artikelnummer4070
TidsskriftNature Communications
Vol/bind12
Udgave nummer1
Antal sider16
ISSN2041-1723
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was supported by the Lundbeck Foundation, the Novo Nordisk Foundation, the European Commission (GlycoImaging H2020-MSCA-ITN-721297, BioCapture H2020-MSCA-ITN-722171), the Danish National Research Foundation (DNRF107), the Mizutani Foundation (to Y.N.), the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement No 787684 (to C.B.), and the National Institutes of Health grant (R01GM32373 to A.V. and GM137458 to T.M.I.).

Publisher Copyright:
© 2021, The Author(s).

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