9KYZ

A35 of MPXV in complex with mAb975

Summary for 9KYZ

• Entry DOI: 10.2210/pdb9kyz/pdb
• EMDB information: 62650
• Descriptor: Protein OPG161, mab975HC, mab975KC (3 entities in total)
• Functional Keywords: envelope glycoprotein, viral protein/immune system, viral protein-immune system complex
• Biological source: Monkeypox virus; More
• Total number of polymer chains: 4
• Total formula weight: 42932.10

Authors

Yan, R.H.,Yang, H.N. (deposition date: 2024-12-09, release date: 2025-08-13, Last modification date: 2025-12-24)

Primary citation

Ju, B.,Liu, C.,Zhang, J.,Li, Y.,Yang, H.,Zhou, B.,Huang, B.,Ma, J.,Lu, J.,Cheng, L.,Cong, Z.,Zhu, L.,Shi, T.,Sun, Y.,Li, N.,Chen, T.,Wang, M.,Tang, S.,Ge, X.,Zhao, J.,Tan, W.J.,Yan, R.,Xue, J.,Zhang, Z.
Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection.
Cell, 188:6253-6265.e14, 2025

PubMed Abstract: The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this study, we demonstrated two human anti-A35 monoclonal antibodies (mAbs) displayed potential protection against MPXV in CAST/EiJ mice and rhesus macaques. Using cryo-electron microscopy, we determined two high-resolution structures of the A35 dimer in complex with the fragment of antigen binding of mAb 975 or mAb 981, revealing detailed interactions at the antigen-antibody interfaces. Structural analysis showed that these structurally conserved mAbs bind to a groove region at the interface of A35 dimer. Overall, we provided a proof of concept for a single administration of anti-A35 mAbs mitigating the pathogenic effects of MPXV infection in rhesus macaques. These human-derived mAbs could be served as antibody drug candidates, and their binding models to the A35 dimer will provide valuable insights for future vaccine design.

PubMed: 40865530
DOI: 10.1016/j.cell.2025.08.005

Experimental method

ELECTRON MICROSCOPY (3.2 Å)