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 de Haan; Renaud Vincentelli; Bernard Henrissat; Sergey Y Vakhrushev; Henrik Clausen; Yoshiki Narimatsu

doi:10.1038/s41467-021-24366-4

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 VriesCornelis A M de Haan, Renaud Vincentelli, Bernard Henrissat, Sergey Y Vakhrushev, Henrik Clausen, Yoshiki Narimatsu

Virology

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	4070
Pages (from-to)	1-16
Number of pages	16
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-24366-4
Publication status	Published - 1 Jul 2021

Bibliographical 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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Cite this

Nason, R., Büll, C., Konstantinidi, A., Sun, L., Ye, Z., Halim, A., Du, W., Sørensen, D. M., Durbesson, F., Furukawa, S., Mandel, U., Joshi, H. J., Dworkin, L. A., Hansen, L., David, L., Iverson, T. M., Bensing, B. A., Sullam, P. M., Varki, A., ... Narimatsu, Y. (2021). Display of the human mucinome with defined O-glycans by gene engineered cells. Nature Communications, 12(1), 1-16. Article 4070. https://doi.org/10.1038/s41467-021-24366-4

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title = "Display of the human mucinome with defined O-glycans by gene engineered cells",

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.",

author = "Rebecca Nason and Christian B{\"u}ll and Andriana Konstantinidi and Lingbo Sun and Zilu Ye and Adnan Halim and Wenjuan Du and S{\o}rensen, {Daniel M} and Fabien Durbesson and Sanae Furukawa and Ulla Mandel and Joshi, {Hiren J} and Dworkin, {Leo Alexander} and Lars Hansen and Leonor David and Iverson, {Tina M} and Bensing, {Barbara A} and Sullam, {Paul M} and Ajit Varki and Vries, {Erik de} and {de Haan}, {Cornelis A M} and Renaud Vincentelli and Bernard Henrissat and Vakhrushev, {Sergey Y} and Henrik Clausen and Yoshiki Narimatsu",

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{\textquoteright}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: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41467-021-24366-4",

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Nason, R, Büll, C, Konstantinidi, A, Sun, L, Ye, Z, Halim, A, Du, W, Sørensen, DM, Durbesson, F, Furukawa, S, Mandel, U, Joshi, HJ, Dworkin, LA, Hansen, L, David, L, Iverson, TM, Bensing, BA, Sullam, PM, Varki, A, Vries, ED , de Haan, CAM, Vincentelli, R, Henrissat, B, Vakhrushev, SY, Clausen, H & Narimatsu, Y 2021, 'Display of the human mucinome with defined O-glycans by gene engineered cells', Nature Communications, vol. 12, no. 1, 4070, pp. 1-16. https://doi.org/10.1038/s41467-021-24366-4

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T1 - Display of the human mucinome with defined O-glycans by gene engineered cells

AU - Nason, Rebecca

AU - Büll, Christian

AU - Konstantinidi, Andriana

AU - Sun, Lingbo

AU - Ye, Zilu

AU - Halim, Adnan

AU - Du, Wenjuan

AU - Sørensen, Daniel M

AU - Durbesson, Fabien

AU - Furukawa, Sanae

AU - Mandel, Ulla

AU - Joshi, Hiren J

AU - Dworkin, Leo Alexander

AU - Hansen, Lars

AU - David, Leonor

AU - Iverson, Tina M

AU - Bensing, Barbara A

AU - Sullam, Paul M

AU - Varki, Ajit

AU - Vries, Erik de

AU - de Haan, Cornelis A M

AU - Vincentelli, Renaud

AU - Henrissat, Bernard

AU - Vakhrushev, Sergey Y

AU - Clausen, Henrik

AU - Narimatsu, Yoshiki

N1 - 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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Display of the human mucinome with defined O-glycans by gene engineered cells

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