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TitleStructure of a zoonotic H5N1 hemagglutinin reveals a receptor-binding site occupied by an auto-glycan.
Journal, issue, pagesStructure, Vol. 33, Issue 2, Page 228-233.e3, Year 2025
Publish dateFeb 6, 2025
AuthorsNicholas C Morano / Yicheng Guo / Jordan E Becker / Zhiteng Li / Jian Yu / David D Ho / Lawrence Shapiro / Peter D Kwong /
PubMed AbstractHighly pathogenic avian influenza has spilled into many mammals, most notably cows and poultry, with several dozen human breakthrough infections. Zoonotic crossovers, with hemagglutinins mutated to ...Highly pathogenic avian influenza has spilled into many mammals, most notably cows and poultry, with several dozen human breakthrough infections. Zoonotic crossovers, with hemagglutinins mutated to enhance viral ability to use human α2-6-linked sialic acid receptors versus avian α2-3-linked ones, highlight the pandemic risk. To gain insight into these crossovers, we determined the cryoelectron microscopy (cryo-EM) structure of the hemagglutinin from the zoonotic H5N1 A/Texas/37/2024 strain (clade 2.3.4.4b) in complex with a previously reported neutralizing antibody. Surprisingly, we found that the receptor-binding site of this H5N1 hemagglutinin was already occupied by an α2-3-linked sialic acid and that this glycan emanated from asparagine N169 of a neighboring protomer on hemagglutinin itself. This structure thus highlights recognition by influenza hemagglutinin of an "auto"-α2-3-linked sialic acid from N169, an N-linked glycan conserved in 95% of H5 strains, and adds "auto-glycan recognition," which may play a role in viral dispersal, to the complexities surrounding H5N1 zoonosis.
External linksStructure / PubMed:39884273
MethodsEM (single particle)
Resolution2.68 Å
Structure data

48120

9ekf

EMDB-48120, PDB-9ekf:
CryoEM structure of H5N1 A/Texas/37/2024 HA bound to Fab 65C6 and an auto glycan occupying the receptor-binding site
Method: EM (single particle) / Resolution: 2.68 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • influenza a virus
KeywordsVIRAL PROTEIN / H5N1 / antibody / influenza

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