SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms.

TitleSARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms.
Publication TypeJournal Article
Year of Publication2021
AuthorsO'Donoghue, SI, Schafferhans, A, Sikta, N, Stolte, C, Kaur, S, Ho, BK, Anderson, S, Procter, JB, Dallago, C, Bordin, N, Adcock, M, Rost, B
JournalMol Syst Biol
Volume17
Issue9
Paginatione10079
Date Published2021 09
ISSN1744-4292
KeywordsAmino Acid Transport Systems, Neutral, Angiotensin-Converting Enzyme 2, Binding Sites, Computational Biology, Coronavirus Envelope Proteins, Coronavirus Nucleocapsid Proteins, COVID-19, 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
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.

DOI10.15252/msb.202010079
Alternate JournalMol Syst Biol
PubMed ID34519429
PubMed Central IDPMC8438690
Grant List01IS17049 / / Bundesministerium für Bildung und Forschung (BMBF) /
031L0168 / / Bundesministerium für Bildung und Forschung (BMBF) /
/ / Tour de Cure Australia /
BB/R009597/1 / / Biotechnology and Biological Sciences Research Council (BBSRC) /
/ WT_ / Wellcome Trust / United Kingdom
218259/Z/19/Z / / Wellcome Trust, UK /
/ / Garvan Research Foundation /
/ / Sony Foundation Australia /