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

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Article number4070
Pages (from-to)1-16
Number of pages16
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 1 Jul 2021

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