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.
Keywords:
COVID-19; SARS-CoV-2; bioinformatics; data visualization; structural biology.
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Transport Systems, Neutral / chemistry
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Amino Acid Transport Systems, Neutral / genetics
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Amino Acid Transport Systems, Neutral / metabolism
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Angiotensin-Converting Enzyme 2 / chemistry
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Angiotensin-Converting Enzyme 2 / genetics
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Angiotensin-Converting Enzyme 2 / metabolism*
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Binding Sites
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COVID-19 / genetics
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COVID-19 / metabolism
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COVID-19 / virology
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Computational Biology / methods
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Coronavirus Envelope Proteins / chemistry
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Coronavirus Envelope Proteins / genetics
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Coronavirus Envelope Proteins / metabolism
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Coronavirus Nucleocapsid Proteins / chemistry
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Coronavirus Nucleocapsid Proteins / genetics
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Coronavirus Nucleocapsid Proteins / metabolism
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Host-Pathogen Interactions / genetics*
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Humans
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Mitochondrial Membrane Transport Proteins / chemistry
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism
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Mitochondrial Precursor Protein Import Complex Proteins
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Models, Molecular
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Molecular Mimicry
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Neuropilin-1 / chemistry
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Neuropilin-1 / genetics
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Neuropilin-1 / metabolism
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Protein Interaction Mapping / methods
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Protein Multimerization
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Protein Processing, Post-Translational*
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SARS-CoV-2 / chemistry
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SARS-CoV-2 / genetics
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SARS-CoV-2 / metabolism*
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / metabolism*
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Viral Matrix Proteins / chemistry
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism
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Viroporin Proteins / chemistry
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Viroporin Proteins / genetics
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Viroporin Proteins / metabolism
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Virus Replication
Substances
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Amino Acid Transport Systems, Neutral
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Coronavirus Envelope Proteins
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Coronavirus Nucleocapsid Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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NRP1 protein, human
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ORF3a protein, SARS-CoV-2
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Phosphoproteins
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SLC6A19 protein, human
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Spike Glycoprotein, Coronavirus
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TOMM70 protein, human
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Viral Matrix Proteins
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Viroporin Proteins
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envelope protein, SARS-CoV-2
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membrane protein, SARS-CoV-2
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nucleocapsid phosphoprotein, SARS-CoV-2
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spike protein, SARS-CoV-2
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Neuropilin-1
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2