Display of the human mucinome with defined O-glycans by gene engineered cells
| Autor: | Paul M. Sullam, Tina M. Iverson, Barbara A. Bensing, Leo Alexander Dworkin, Henrik Clausen, Daniel Madriz Sørensen, Ajit Varki, Sanae Furukawa, Cornelis A. M. de Haan, Fabien Durbesson, Lars Hansen, Rebecca Nason, Yoshiki Narimatsu, Leonor David, Bernard Henrissat, Sergey Y. Vakhrushev, Zilu Ye, Ulla Mandel, Andriana Konstantinidi, Hiren J. Joshi, Adnan Halim, Renaud Vincentelli, Erik de Vries, Christian Büll, Lingbo Sun, Wenjuan Du |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde, Virologie, dI&I I&I-1 |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Glycosylation Chemistry(all) Mucin-1 / metabolismo Glycobiology General Physics and Astronomy Biochemistry chemistry.chemical_compound Mucin-1 / genetics Polysaccharides / genetics chemistry.chemical_classification Multidisciplinary Mucous Membrane / metabolism Microbiota 3. Good health Cell biology lipids (amino acids peptides and proteins) Genetic Engineering hormones hormone substitutes and hormone antagonists Mucins / metabolism endocrine system animal structures Science Physics and Astronomy(all) General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Rare Diseases Tandem repeat Polysaccharides Polysaccharides / metabolism Humans Microbiome Glycoproteins Mucous Membrane 030102 biochemistry & molecular biology Biochemistry Genetics and Molecular Biology(all) HEK 293 cells Mucin Mucin-1 Mucins General Chemistry Bacterial adhesin carbohydrates (lipids) 030104 developmental biology HEK293 Cells chemistry Genetic engineering Glycoprotein Genetics and Molecular Biology(all) |
| Zdroj: | 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, Vries, E D, de Haan, C A M, Vincentelli, R, Henrissat, B, Vakhrushev, S Y, 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 . https://doi.org/10.1038/s41467-021-24366-4 Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) Nature Communications Nature Communications, 12(1), 1. Nature Publishing Group Nature communications, vol 12, iss 1 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-24366-4 |
| Popis: | 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. Mucins play critical roles in maintaining the human microbiome, with their O-glycosylated tandem repeats (TRs) providing important cues for microbiota. Here, the authors develop a cellular platform for producing TRs with defined O-glycan structures to dissect the functions of TR O-glycosylation. |
| Databáze: | OpenAIRE |
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