9DSC

Crystal structure of Apo-241_2F04-A95a mutant Fab

Summary for 9DSC

• Entry DOI: 10.2210/pdb9dsc/pdb
• Descriptor: 241_2F04-A95a, Heavy chain, 241_2F04-A95a, Light chain (3 entities in total)
• Functional Keywords: antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 95134.32

Authors

Lin, T.H.,Wilson, I.A. (deposition date: 2024-09-26, release date: 2025-03-19)

Primary citation

Lin, T.H.,Lee, C.D.,Fernandez-Quintero, M.L.,Ferguson, J.A.,Han, J.,Zhu, X.,Yu, W.,Guthmiller, J.J.,Krammer, F.,Wilson, P.C.,Ward, A.B.,Wilson, I.A.
Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of V H 3 and V K 3 genes.
Nat Commun, 16:1268-1268, 2025

PubMed Abstract: H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their V and V genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.

PubMed: 39894881
DOI: 10.1038/s41467-025-56496-4

Experimental method

X-RAY DIFFRACTION (2.01 Å)