9I42

Structure of anti-EV71 human monoclonal antibody 16-2-2D Fab

Summary for 9I42

• Entry DOI: 10.2210/pdb9i42/pdb
• Descriptor: light chain 1, heavy chain 1, SULFATE ION, ... (6 entities in total)
• Functional Keywords: ev71, antibody, 16-2-2d, fab, antiviral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 100437.33

Authors

Zhou, D.,Ren, J.,Stuart, D.I. (deposition date: 2025-01-24, release date: 2026-02-04, Last modification date: 2026-06-17)

Primary citation

Zhou, D.,Kotecha, A.,Kelly, J.T.,Huang, P.N.,Chen, Y.Y.,Walter, T.S.,Duyvesteyn, H.M.E.,Owens, R.J.,Ho, S.Y.,Lin, T.Y.,Fry, E.E.,Ren, J.,Huang, K.A.,Stuart, D.I.
Structural and functional mapping of protective human monoclonal antibodies against enterovirus A71.
Sci Adv, 12:eaee8217-eaee8217, 2026

PubMed Abstract: EV-A71 has been responsible for recent severe HFMD outbreaks. We report structures for 12 potently neutralizing human anti-EV-A71 monoclonal antibody Fabs, alone and complexed with virus. Most recognize the native antigenic state with epitopes that span interfaces, together covering 85% of the capsid surface. The majority (8 of 12) bind the canyon, while the others cluster around the icosahedral two- and threefold axes. Blocking SCARB2 receptor binding likely contributes to neutralization for all, and a subset induces empty particles. A predominant gene family (IGHV4-39) does not dictate a common binding pose. Long CDR-H3 loops are frequently key to binding, especially at the canyon, suggesting that antigenicity data based on antibodies with shorter CDR3s (e.g., murine) may be misleading. This dataset reveals neutralization mechanisms for recently circulating EV-A71 genotypes, which will inform immunotherapies. We demonstrate synergy in vitro between canyon binding and both two- and threefold binding antibodies to increase neutralization potency.

PubMed: 42247493
DOI: 10.1126/sciadv.aee8217

Experimental method

X-RAY DIFFRACTION (1.92 Å)