9P3Y

Andes virus glycoprotein tetramer in complex with ADI-65534 Fab

This is a non-PDB format compatible entry.

Summary for 9P3Y

• Entry DOI: 10.2210/pdb9p3y/pdb
• EMDB information: 71259
• Descriptor: ADI-65534 variable heavy chain, ADI-65534 variable light chain, Glycoprotein N, ... (7 entities in total)
• Functional Keywords: gn/gc, tetramer, hantavirus, prefusion, antibody, neutralizing, quaternary epitope, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 666459.78

Authors

McFadden, E.,Guo, L.,McLellan, J.S. (deposition date: 2025-06-14, release date: 2025-07-30)

Primary citation

Guo, L.,McFadden, E.,Slough, M.M.,Taylor Stone, E.,Berrigan, J.,Mittler, E.,Hatzakis, K.,Hinkley, T.,Kain, H.S.,Ke, Z.,Warner, N.L.,Erasmus, J.H.,Chandran, K.,McLellan, J.S.
High-resolution in situ structures of hantavirus glycoprotein tetramers.
Biorxiv, 2025

PubMed Abstract: New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This enabled the determination of a 2.35 Å resolution structure of the membrane-embedded Andes virus (ANDV) glycoprotein tetramer, as well as structures of dimers of tetramers and a complex with antibody ADI-65534. These structures reveal previously uncharacterized features of glycoprotein organization, stability, and pH-sensing. Immunization of mice with self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies compared to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts.

PubMed: 40667040
DOI: 10.1101/2025.06.17.660152

Experimental method

ELECTRON MICROSCOPY (3.3 Å)