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TitleMolecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateDec 22, 2020
AuthorsIlona 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 AbstractThe 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.
External linksElife / PubMed:33349334 / PubMed Central
MethodsEM (subtomogram averaging) / X-ray diffraction
Resolution3.5 - 14.3 Å
Structure data

11964

7b09

EMDB-11964: Puumala virus-like particle glycoprotein spike in complex with fab fragment P-4G2.
PDB-7b09: Puumala virus glycoprotein (Gc) in complex with fab fragment P-4G2.
Method: EM (subtomogram averaging) / Resolution: 13.4 Å

EMDB-11965:
A reconstruction of Puumala virus-like particle glycoprotein spike lattice in the presence of fab 4G2 which is absent from the reconstruction.
Method: EM (subtomogram averaging) / Resolution: 14.3 Å

11966

7b0a

EMDB-11966: Puumala virus-like particle glycoprotein lattice.
PDB-7b0a: Puumala virus-like particle glycoprotein spike and lattice contacts model.
Method: EM (subtomogram averaging) / Resolution: 13.9 Å

PDB-6z06:
Crystal structure of Puumala virus Gc in complex with Fab 4G2
Method: X-RAY DIFFRACTION / Resolution: 3.5 Å

Chemicals

ChemComp-GOL:
GLYCEROL

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • myodes glareolus (Bank vole)
  • puumala orthohantavirus
KeywordsVIRAL PROTEIN / viral glycoprotein / class II fusion glycoprotein / neutralizing antibody complex / hantavirus glycoprotein Gc / bank vole antibody / VIRUS LIKE PARTICLE / VLP / virus-like particle / Puumala / PUUV / glycoprotein / spike / fab / P-4G2 / antibody / epitope

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