8E8Z

9H2 Fab-Sabin poliovirus 1 complex

Summary for 8E8Z

• Entry DOI: 10.2210/pdb8e8z/pdb
• EMDB information: 27943 27947 27948 27949 27950 27951
• Descriptor: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3, ... (6 entities in total)
• Functional Keywords: complex, fab, poliovirus, neutralizing, virus-immune system complex, virus/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 119672.55

Authors

Charnesky, A.J. (deposition date: 2022-08-26, release date: 2023-06-21, Last modification date: 2024-10-23)

Primary citation

Charnesky, A.J.,Faust, J.E.,Lee, H.,Puligedda, R.D.,Goetschius, D.J.,DiNunno, N.M.,Thapa, V.,Bator, C.M.,Cho, S.H.J.,Wahid, R.,Mahmood, K.,Dessain, S.,Chumakov, K.M.,Rosenfeld, A.,Hafenstein, S.L.
A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes.
Nat Commun, 14:6335-6335, 2023

PubMed Abstract: Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.

PubMed: 37816742
DOI: 10.1038/s41467-023-41052-9

Experimental method

ELECTRON MICROSCOPY (3.15 Å)