24KR

Structural basis of influenza A virus neutralization by broadly active single-domain antibody G2.3 recognizing glycosylated epitope within hemagglutinin stem

Summary for 24KR

• Entry DOI: 10.2210/pdb24kr/pdb
• EMDB information: 69590
• Descriptor: Hemagglutinin, Heavy chain antibody G2.3-Fc, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: hemagglutinin, influenza a, h1n1, antibody, g2.3, cryoem, stem domain, antiviral protein
• Biological source: Influenza A virus (A/California/04/2009(H1N1)); More
• Total number of polymer chains: 6
• Total formula weight: 326224.05

Authors

Ilyasov, I.O.,Baymukhametov, T.N.,Voronina, D.V.,Vorobiev, I.I.,Khodak, Y.A.,Burtseva, A.D.,Popov, V.O.,Sluchanko, N.N.,Shcheblyakov, D.V.,Boyko, K.M. (deposition date: 2026-03-08, release date: 2026-06-10)

Primary citation

Ilyasov, I.O.,Voronina, D.V.,Baymukhametov, T.N.,Vorobiev, I.I.,Ryabova, E.I.,Derkaev, A.A.,Esmagambetov, I.B.,Shmarov, M.M.,Khodak, Y.A.,Burtseva, A.D.,Sluchanko, N.N.,Boyko, K.M.,Shcheblyakov, D.V.,Gintsburg, A.L.,Popov, V.O.,Logunov, D.Y.
Structural basis of influenza A virus neutralization by broadly reactive single-domain antibody G2.3 recognizing glycosylated epitope within hemagglutinin stem domain.
Int.J.Biol.Macromol., :152701-152701, 2026

PubMed Abstract: Influenza remains one of the most common and contagious respiratory infections causing around a billion cases of seasonal illness annually and five million cases of severe consequences. A recently reported G2.3 antibody exhibited a potent cross-subtype activity against Group 1 influenza A viruses. Here, we shed light on the structural basis of the broad neutralizing activity of G2.3 by using cryoEM. Structural analysis of the G2.3 complex with H1 hemagglutinin revealed a partly conserved epitope located on the stem domain. The structural data were confirmed by the assessment of binding and neutralizing properties of the Fc-modified form of G2.3 with a broad panel of recombinant hemagglutinins and influenza A viruses. We demonstrated remarkably high activity of G2.3-Fc against H1N1 viral strains, which is consistent with G2.3 epitope being the most conserved within the H1 subtype, but low activity towards Group 2 of HA, which was explained by the analysis of the epitope. To suggest the mechanism of G2.3 neutralization, we compared its epitope with those of other broadly neutralizing antibodies that attack the stem domain. Finally, we obtained an escape mutant that has two mutations within the epitope and around, unseen in circulating H1 strains, allowing this mutant to elude from G2.3 and made assumption of the mechanism of such evasion.

PubMed: 42190777
DOI: 10.1016/j.ijbiomac.2026.152701

Experimental method

ELECTRON MICROSCOPY (2.53 Å)