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SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms.
O'Donoghue, Seán I; Schafferhans, Andrea; Sikta, Neblina; Stolte, Christian; Kaur, Sandeep; Ho, Bosco K; Anderson, Stuart; Procter, James B; Dallago, Christian; Bordin, Nicola; Adcock, Matt; Rost, Burkhard.
  • O'Donoghue SI; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Schafferhans A; CSIRO Data61, Canberra, ACT, Australia.
  • Sikta N; School of Biotechnology and Biomolecular Sciences (UNSW), Kensington, NSW, Australia.
  • Stolte C; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Kaur S; Department of Bioengineering Sciences, Weihenstephan-Tr. University of Applied Sciences, Freising, Germany.
  • Ho BK; Department of Informatics, Bioinformatics & Computational Biology, Technical University of Munich, Munich, Germany.
  • Anderson S; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Procter JB; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Dallago C; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Bordin N; School of Biotechnology and Biomolecular Sciences (UNSW), Kensington, NSW, Australia.
  • Adcock M; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Rost B; CSIRO Data61, Canberra, ACT, Australia.
Mol Syst Biol ; 17(9): e10079, 2021 09.
Article in English | MEDLINE | ID: covidwho-1406892
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.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism; Host-Pathogen Interactions/genetics; Protein Processing, Post-Translational; SARS-CoV-2/metabolism; Spike Glycoprotein, Coronavirus/metabolism; 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
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Processing, Post-Translational / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Language: English Journal: Mol Syst Biol Journal subject: Molecular Biology / Biotechnology Year: 2021 Document Type: Article Affiliation country: Msb.202010079

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Processing, Post-Translational / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Language: English Journal: Mol Syst Biol Journal subject: Molecular Biology / Biotechnology Year: 2021 Document Type: Article Affiliation country: Msb.202010079