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Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
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- Rissanen, Ilona (author)
- Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford, England.;Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, Helsinki, Finland.
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- Stass, Robert (author)
- Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford, England.
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- Krumm, Stefanie A. (author)
- Kings Coll London, Guys Hosp, Dept Infect Dis, London, England.
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- Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford, England;Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.;Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, Helsinki, Finland. Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford, England. (creator_code:org_t)
- eLife Sciences Publications, Ltd, 2020
- 2020
- English.
- In: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 9
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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, cryoelectron 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)(4) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- Rissanen, Ilona
- Stass, Robert
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- Seow, Jeffrey
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- Paesen, Guido C.
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- Hepojoki, Jussi
- Vapalahti, Olli
- Lundkvist, Åke
- Reynard, Olivier
- Volchkov, Viktor
- Doores, Katie J.
- Huiskonen, Juha ...
- Bowden, Thomas A ...
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- MEDICAL AND HEALTH SCIENCES
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- and Basic Medicine
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- eLIFE
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- Uppsala University
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