Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry
Abstract Following endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K+] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical...
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Nature Portfolio
2023-09-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-41205-w |
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author | Samantha Hover Frank W. Charlton Jan Hellert Jessica J. Swanson Jamel Mankouri John N. Barr Juan Fontana |
author_facet | Samantha Hover Frank W. Charlton Jan Hellert Jessica J. Swanson Jamel Mankouri John N. Barr Juan Fontana |
author_sort | Samantha Hover |
collection | DOAJ |
description | Abstract Following endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K+] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical bunyavirus. Here, we use sub-tomogram averaging and AlphaFold, to generate a pseudo-atomic model of the whole BUNV glycoprotein envelope. We unambiguously locate the Gc fusion domain and its chaperone Gn within the floor domain of the spike. Furthermore, viral incubation at low pH and high [K+], reminiscent of endocytic conditions, results in a dramatic rearrangement of the BUNV envelope. Structural and biochemical assays indicate that pH 6.3/K+ in the absence of a target membrane elicits a fusion-capable triggered intermediate state of BUNV GPs; but the same conditions induce fusion when target membranes are present. Taken together, we provide mechanistic understanding of the requirements for bunyavirus entry. |
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issn | 2041-1723 |
language | English |
last_indexed | 2024-03-10T17:34:26Z |
publishDate | 2023-09-01 |
publisher | Nature Portfolio |
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spelling | doaj.art-89f71ba3dc2a4843a816c001509db6072023-11-20T09:53:58ZengNature PortfolioNature Communications2041-17232023-09-0114111610.1038/s41467-023-41205-wOrganisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entrySamantha Hover0Frank W. Charlton1Jan Hellert2Jessica J. Swanson3Jamel Mankouri4John N. Barr5Juan Fontana6School of Molecular and Cellular Biology, Faculty of Biological SciencesSchool of Molecular and Cellular Biology, Faculty of Biological SciencesCentre for Structural Systems Biology, Leibniz-Institut für Virologie (LIV)School of Molecular and Cellular Biology, Faculty of Biological SciencesSchool of Molecular and Cellular Biology, Faculty of Biological SciencesSchool of Molecular and Cellular Biology, Faculty of Biological SciencesSchool of Molecular and Cellular Biology, Faculty of Biological SciencesAbstract Following endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K+] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical bunyavirus. Here, we use sub-tomogram averaging and AlphaFold, to generate a pseudo-atomic model of the whole BUNV glycoprotein envelope. We unambiguously locate the Gc fusion domain and its chaperone Gn within the floor domain of the spike. Furthermore, viral incubation at low pH and high [K+], reminiscent of endocytic conditions, results in a dramatic rearrangement of the BUNV envelope. Structural and biochemical assays indicate that pH 6.3/K+ in the absence of a target membrane elicits a fusion-capable triggered intermediate state of BUNV GPs; but the same conditions induce fusion when target membranes are present. Taken together, we provide mechanistic understanding of the requirements for bunyavirus entry.https://doi.org/10.1038/s41467-023-41205-w |
spellingShingle | Samantha Hover Frank W. Charlton Jan Hellert Jessica J. Swanson Jamel Mankouri John N. Barr Juan Fontana Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry Nature Communications |
title | Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry |
title_full | Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry |
title_fullStr | Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry |
title_full_unstemmed | Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry |
title_short | Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry |
title_sort | organisation of the orthobunyavirus tripodal spike and the structural changes induced by low ph and k during entry |
url | https://doi.org/10.1038/s41467-023-41205-w |
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