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

Authors :
O'Donoghue SI
Schafferhans A
Sikta N
Stolte C
Kaur S
Ho BK
Anderson S
Procter JB
Dallago C
Bordin N
Adcock M
Rost B
Source :
Molecular systems biology [Mol Syst Biol] 2021 Sep; Vol. 17 (9), pp. e10079.
Publication Year :
2021

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.<br /> (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Subjects

Subjects :
Amino Acid Transport Systems, Neutral chemistry
Amino Acid Transport Systems, Neutral genetics
Amino Acid Transport Systems, Neutral metabolism
Angiotensin-Converting Enzyme 2 chemistry
Angiotensin-Converting Enzyme 2 genetics
Binding Sites
COVID-19 genetics
COVID-19 metabolism
COVID-19 virology
Computational Biology methods
Coronavirus Envelope Proteins chemistry
Coronavirus Envelope Proteins genetics
Coronavirus Envelope Proteins metabolism
Coronavirus Nucleocapsid Proteins chemistry
Coronavirus Nucleocapsid Proteins genetics
Coronavirus Nucleocapsid Proteins metabolism
Humans
Mitochondrial Membrane Transport Proteins chemistry
Mitochondrial Membrane Transport Proteins genetics
Mitochondrial Membrane Transport Proteins metabolism
Mitochondrial Precursor Protein Import Complex Proteins
Models, Molecular
Molecular Mimicry
Neuropilin-1 chemistry
Neuropilin-1 genetics
Neuropilin-1 metabolism
Phosphoproteins chemistry
Phosphoproteins genetics
Phosphoproteins metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Interaction Mapping methods
Protein Multimerization
SARS-CoV-2 chemistry
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus chemistry
Spike Glycoprotein, Coronavirus genetics
Viral Matrix Proteins chemistry
Viral Matrix Proteins genetics
Viral Matrix Proteins metabolism
Viroporin Proteins chemistry
Viroporin Proteins genetics
Viroporin Proteins metabolism
Virus Replication
Angiotensin-Converting Enzyme 2 metabolism
Host-Pathogen Interactions genetics
Protein Processing, Post-Translational
SARS-CoV-2 metabolism
Spike Glycoprotein, Coronavirus metabolism

Details

Language :
English
ISSN :
1744-4292
Volume :
17
Issue :
9
Database :
MEDLINE
Journal :
Molecular systems biology
Publication Type :
Academic Journal
Accession number :
34519429
Full Text :
https://doi.org/10.15252/msb.202010079