O'Donoghue, SI;
Schafferhans, A;
Sikta, N;
Stolte, C;
Kaur, S;
Ho, BK;
Anderson, S;
... Rost, B; + view all
(2021)
SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms.
Molecular Systems Biology
, 17
(9)
, Article e10079. 10.15252/msb.202010079.
Preview |
Text
Bordin_msb.202010079.pdf - Published Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/msb.202010079 |
| Publisher version: | https://doi.org/10.15252/msb.202010079 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | COVID-19, SARS-CoV-2, bioinformatics, data visualization, structural biology, Amino Acid Transport Systems, Neutral, Angiotensin-Converting Enzyme 2, Binding Sites, COVID-19, Computational Biology, Coronavirus Envelope Proteins, Coronavirus Nucleocapsid Proteins, Host-Pathogen Interactions, Humans, Mitochondrial Membrane Transport Proteins, Models, Molecular, Molecular Mimicry, Neuropilin-1, Phosphoproteins, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Protein Multimerization, Protein Processing, Post-Translational, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Viral Matrix Proteins, Viroporin Proteins, Virus Replication |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10135894 |
Archive Staff Only
 |
View Item |
