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-Structure paper
タイトル | Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein. |
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ジャーナル・号・ページ | Elife, Vol. 9, Year 2020 |
掲載日 | 2020年12月22日 |
著者 | 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 要旨 | 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. |
リンク | Elife / PubMed:33349334 / PubMed Central |
手法 | EM (サブトモグラム平均) / X線回折 |
解像度 | 3.5 - 14.3 Å |
構造データ | 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: |
化合物 | ChemComp-GOL: ChemComp-NAG: |
由来 |
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キーワード | VIRAL 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 |