9CXT

Hemagglutinin A/Hong Kong/1/68 produced in GnTI- cells

Summary for 9CXT

• Entry DOI: 10.2210/pdb9cxt/pdb
• EMDB information: 45997
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain,Green fluorescent protein fusion, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: hemagglutinin, glycoprotein, viral protein
• Biological source: Influenza A virus (strain A/Hong Kong/1/1968 H3N2); More
• Total number of polymer chains: 6
• Total formula weight: 287773.45

Authors

Torrents de la Pena, A.,de Paiva Froes Rocha, R.,Ward, A.B. (deposition date: 2024-07-31, release date: 2025-08-06, Last modification date: 2025-12-24)

Primary citation

de Paiva Froes Rocha, R.,Tomris, I.,Bowman, C.A.,Stevens, E.,Kantorow, J.,Plitt, C.M.,Peng, W.,Oeverdieck, S.,Galdino Andrade, T.,Ferguson, J.A.,Jung, D.D.,Marques, R.E.,Herfst, S.,Snijder, J.,Chakraborty, S.,Torrents de la Pena, A.,Berndsen, Z.T.,de Vries, R.P.,Ward, A.B.
Structural and immunological characterization of the H3 influenza hemagglutinin during antigenic drift.
Nat Commun, 2025

PubMed Abstract: The quest for a universal influenza vaccine holds great promise for mitigating the global burden of influenza-related morbidity and mortality. However, challenges persist in identifying conserved epitopes capable of eliciting robust and durable immune responses. In this study, we explore the influence of glycan evolution on H3 hemagglutinin from 1968 to present day and its impacts on protein structure, antigenicity and immunogenicity by using computational, biochemical and biophysical techniques. Structural characterization of HK/68 and Sing/16 by cryo-electron microscopy shows that while HK/68 is resistant to enzymatic deglycosylation, removal of glycans destabilizes the hyperglycosylated head and membrane-proximal region in Sing/16. Furthermore, the appearance of glycans in Sing/16 hemagglutinin head domain shifts the polyclonal immune response upon vaccination to target the esterase and stem. These insights expand our understanding of glycans beyond their role in protein folding and highlight the interplay among glycan integration and immune recognition to design a universal influenza vaccine.

PubMed: 41381528
DOI: 10.1038/s41467-025-66375-7

Experimental method

ELECTRON MICROSCOPY (3.4 Å)