8X2C

Crystal structure of H5 hemagglutinin from swan-infecting H5N8 influenza virus

Summary for 8X2C

• Entry DOI: 10.2210/pdb8x2c/pdb
• Descriptor: Hemagglutinin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: viral protein
• Biological source: Influenza A virus
• Total number of polymer chains: 3
• Total formula weight: 175306.03

Authors

Jin, X.Y.,Han, P.,Song, H.,Qi, J.X. (deposition date: 2023-11-09, release date: 2025-05-14, Last modification date: 2026-07-01)

Primary citation

Jin, X.,Han, P.,Wang, Y.,Wang, H.,Zhang, C.,Di Maio, A.,Yu, J.,Hao, T.,Gu, Y.,Zhang, Z.,Zhang, W.,Qi, J.,Bi, Y.,Zhang, X.,Sun, L.,Wang, N.,Liu, Y.,Song, H.,Gao, G.F.
Hemagglutinin double-mutation enhances binding of human-infecting avian influenza virus clade 2.3.4.4b H5Ny to human and SLe X receptors.
Embo Rep., 2026

PubMed Abstract: Clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) continue to circulate worldwide, posing zoonotic threats, especially with recent cattle outbreaks. The mechanisms by which these viruses adapt to mammalian hosts while maintaining a broad avian tropism remain poorly understood. Here, we demonstrate that two naturally occurring mutations (K222Q and S227R) in the hemagglutinin (HA) of a human-infecting H5N8 strain, first identified in 2020, enhance binding affinity for both α2-6-linked and Sialyl Lewis (SLe) glycans, which may underlie the broad tissue binding and cross-species potential. Structural analyses reveal that these mutations expand receptor specificity for these glycans, which are abundant in the human respiratory tract and duck trachea, providing a possible molecular basis for cross-species transmission. Our findings suggest that clade 2.3.4.4b H5Ny viruses evolved dual receptor specificity as early as the 2020 Russian H5N8 strain, potentially contributing to sporadic human infections and widespread dissemination among birds and mammals.

PubMed: 42303811
DOI: 10.1038/s44319-026-00816-2

Experimental method

X-RAY DIFFRACTION (2.59 Å)