Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function

M. Osman Sheikh, Chantelle J. Capicciotti, Lin Liu, Jeremy Praissman, Dahai Ding, Daniel G. Mead, Melinda A. Brindley, Tobias Willer, Kevin P. Campbell, Kelley W. Moremen, Lance Wells () and Geert-Jan Boons ()
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M. Osman Sheikh: University of Georgia
Chantelle J. Capicciotti: University of Georgia
Lin Liu: University of Georgia
Jeremy Praissman: University of Georgia
Dahai Ding: University of Georgia
Daniel G. Mead: University of Georgia
Melinda A. Brindley: University of Georgia
Tobias Willer: The University of Iowa
Kevin P. Campbell: The University of Iowa
Kelley W. Moremen: University of Georgia
Lance Wells: University of Georgia
Geert-Jan Boons: University of Georgia

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity.

Date: 2022
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DOI: 10.1038/s41467-022-31205-7

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