SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms
Abstract We modeled 3D structures of all SARS‐CoV‐2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post‐transla...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2021-09-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202010079 |
| _version_ | 1797282288366518272 |
|---|---|
| author | Seán I O’Donoghue Andrea Schafferhans Neblina Sikta Christian Stolte Sandeep Kaur Bosco K Ho Stuart Anderson James B Procter Christian Dallago Nicola Bordin Matt Adcock Burkhard Rost |
| author_facet | Seán I O’Donoghue Andrea Schafferhans Neblina Sikta Christian Stolte Sandeep Kaur Bosco K Ho Stuart Anderson James B Procter Christian Dallago Nicola Bordin Matt Adcock Burkhard Rost |
| author_sort | Seán I O’Donoghue |
| collection | DOAJ |
| description | Abstract We modeled 3D structures of all SARS‐CoV‐2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post‐translational modifications, block host translation, and disable host defenses; a further ˜29% self‐assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is—and is not—known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria‐COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark. |
| first_indexed | 2024-03-07T17:10:41Z |
| format | Article |
| id | doaj.art-57f25c5fa4df43d2b612f9be089e03cc |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:10:41Z |
| publishDate | 2021-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-57f25c5fa4df43d2b612f9be089e03cc2024-03-03T01:02:25ZengSpringer NatureMolecular Systems Biology1744-42922021-09-01179n/an/a10.15252/msb.202010079SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanismsSeán I O’Donoghue0Andrea Schafferhans1Neblina Sikta2Christian Stolte3Sandeep Kaur4Bosco K Ho5Stuart Anderson6James B Procter7Christian Dallago8Nicola Bordin9Matt Adcock10Burkhard Rost11Garvan Institute of Medical Research Darlinghurst NSW AustraliaGarvan Institute of Medical Research Darlinghurst NSW AustraliaGarvan Institute of Medical Research Darlinghurst NSW AustraliaGarvan Institute of Medical Research Darlinghurst NSW AustraliaGarvan Institute of Medical Research Darlinghurst NSW AustraliaGarvan Institute of Medical Research Darlinghurst NSW AustraliaCSIRO Data61 Canberra ACT AustraliaSchool of Life Sciences The University of Dundee Dundee UKDepartment of Informatics Bioinformatics & Computational Biology Technical University of Munich Munich GermanyInstitute of Structural and Molecular Biology University College London London UKCSIRO Data61 Canberra ACT AustraliaDepartment of Informatics Bioinformatics & Computational Biology Technical University of Munich Munich GermanyAbstract We modeled 3D structures of all SARS‐CoV‐2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post‐translational modifications, block host translation, and disable host defenses; a further ˜29% self‐assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is—and is not—known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria‐COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark.https://doi.org/10.15252/msb.202010079bioinformaticsCOVID‐19data visualizationSARS‐CoV‐2structural biology |
| spellingShingle | Seán I O’Donoghue Andrea Schafferhans Neblina Sikta Christian Stolte Sandeep Kaur Bosco K Ho Stuart Anderson James B Procter Christian Dallago Nicola Bordin Matt Adcock Burkhard Rost SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms Molecular Systems Biology bioinformatics COVID‐19 data visualization SARS‐CoV‐2 structural biology |
| title | SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| title_full | SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| title_fullStr | SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| title_full_unstemmed | SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| title_short | SARS‐CoV‐2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| title_sort | sars cov 2 structural coverage map reveals viral protein assembly mimicry and hijacking mechanisms |
| topic | bioinformatics COVID‐19 data visualization SARS‐CoV‐2 structural biology |
| url | https://doi.org/10.15252/msb.202010079 |
| work_keys_str_mv | AT seaniodonoghue sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT andreaschafferhans sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT neblinasikta sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT christianstolte sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT sandeepkaur sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT boscokho sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT stuartanderson sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT jamesbprocter sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT christiandallago sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT nicolabordin sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT mattadcock sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms AT burkhardrost sarscov2structuralcoveragemaprevealsviralproteinassemblymimicryandhijackingmechanisms |