9NR5

Crystal structure of H5 hemagglutinin Q226L mutant from the influenza virus A/black swan/Akita/1/2016 with LSTc

Summary for 9NR5

• Entry DOI: 10.2210/pdb9nr5/pdb
• Related PRD ID: PRD_900046
• Descriptor: Hemagglutinin HA1, Hemagglutinin HA2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: h1n1, antibody, hemagglutinin, viral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 6
• Total formula weight: 176066.72

Authors

Lin, T.H.,Zhu, Y.,Wilson, I.A. (deposition date: 2025-03-14, release date: 2025-04-23, Last modification date: 2025-04-30)

Primary citation

Rios Carrasco, M.,Lin, T.H.,Zhu, X.,Gabarroca Garcia, A.,Uslu, E.,Liang, R.,Spruit, C.M.,Richard, M.,Boons, G.J.,Wilson, I.A.,de Vries, R.P.
The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors.
Proc.Natl.Acad.Sci.USA, 122:e2419800122-e2419800122, 2025

PubMed Abstract: H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naïve to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, X-ray structural analyses, tissue- and direct glycan binding, we show that L133a Δ and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2016 2.3.4.4b HA was not easily converted to human-type receptor specificity.

PubMed: 40232794
DOI: 10.1073/pnas.2419800122

Experimental method

X-RAY DIFFRACTION (2.52 Å)