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Title | Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein. |
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Journal, issue, pages | Elife, Vol. 9, Year 2020 |
Publish date | Dec 22, 2020 |
![]() | Ilona Rissanen / Robert Stass / Stefanie A Krumm / Jeffrey Seow / Ruben Jg Hulswit / Guido C Paesen / Jussi Hepojoki / Olli Vapalahti / Åke Lundkvist / Olivier Reynard / Viktor Volchkov / Katie J Doores / Juha T Huiskonen / Thomas A Bowden / ![]() ![]() ![]() ![]() ![]() |
PubMed Abstract | The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. ...The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryo-electron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses. |
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Methods | EM (subtomogram averaging) / X-ray diffraction |
Resolution | 3.5 - 14.3 Å |
Structure data | EMDB-11964: Puumala virus-like particle glycoprotein spike in complex with fab fragment P-4G2. ![]() EMDB-11965: EMDB-11966: Puumala virus-like particle glycoprotein lattice. ![]() PDB-6z06: |
Chemicals | ![]() ChemComp-GOL: ![]() ChemComp-NAG: |
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