tetano
Editor, Senior Moderator
Nat Commun
. 2024 Apr 6;15(1):2979.
doi: 10.1038/s41467-024-47344-y. Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling
Luca Unione[SUP] 1 2 3 [/SUP], Augustinus N A Ammerlaan[SUP] 4 [/SUP], Gerlof P Bosman[SUP] 4 [/SUP], Elif Uslu[SUP] 4 [/SUP], Ruonan Liang[SUP] 4 [/SUP], Frederik Broszeit[SUP] 4 [/SUP], Roosmarijn van der Woude[SUP] 4 [/SUP], Yanyan Liu[SUP] 4 [/SUP], Shengzhou Ma[SUP] 5 [/SUP], Lin Liu[SUP] 5 [/SUP], Marcos Gómez-Redondo[SUP] 6 [/SUP], Iris A Bermejo[SUP] 6 [/SUP], Pablo Valverde[SUP] 6 [/SUP], Tammo Diercks[SUP] 6 [/SUP], Ana Ardá[SUP] 6 7 [/SUP], Robert P de Vries[SUP] 8 [/SUP], Geert-Jan Boons[SUP] 9 10 11 12 [/SUP]
Affiliations
Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin's (HAs) are examined by chemoenzymatic synthesis of N-glycans having [SUP]13[/SUP]C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-[SUP]1[/SUP]H by [SUP]13[/SUP]C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.
. 2024 Apr 6;15(1):2979.
doi: 10.1038/s41467-024-47344-y. Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling
Luca Unione[SUP] 1 2 3 [/SUP], Augustinus N A Ammerlaan[SUP] 4 [/SUP], Gerlof P Bosman[SUP] 4 [/SUP], Elif Uslu[SUP] 4 [/SUP], Ruonan Liang[SUP] 4 [/SUP], Frederik Broszeit[SUP] 4 [/SUP], Roosmarijn van der Woude[SUP] 4 [/SUP], Yanyan Liu[SUP] 4 [/SUP], Shengzhou Ma[SUP] 5 [/SUP], Lin Liu[SUP] 5 [/SUP], Marcos Gómez-Redondo[SUP] 6 [/SUP], Iris A Bermejo[SUP] 6 [/SUP], Pablo Valverde[SUP] 6 [/SUP], Tammo Diercks[SUP] 6 [/SUP], Ana Ardá[SUP] 6 7 [/SUP], Robert P de Vries[SUP] 8 [/SUP], Geert-Jan Boons[SUP] 9 10 11 12 [/SUP]
Affiliations
- PMID: 38582892
- PMCID: PMC10998905
- DOI: 10.1038/s41467-024-47344-y
Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin's (HAs) are examined by chemoenzymatic synthesis of N-glycans having [SUP]13[/SUP]C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-[SUP]1[/SUP]H by [SUP]13[/SUP]C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.