Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein
The molecular basis for the severity and rapid spread of the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SA...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2021-01, Vol.118 (2), p.1-6 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Flower, Thomas G. Buffalo, Cosmo Z. Hooy, Richard M. Allaire, Marc Ren, Xuefeng Hurley, James H. |
| description | The molecular basis for the severity and rapid spread of the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SARS-CoV-2 ORF8 was determined at 2.04-Å resolution by X-ray crystallography. The structure reveals a ∼60-residue core similar to SARS-CoV-2 ORF7a, with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. A covalent disulfide-linked dimer is formed through an N-terminal sequence specific to SARS-CoV-2, while a separate noncovalent interface is formed by another SARS-CoV-2−specific sequence, 73YIDI76. Together, the presence of these interfaces shows how SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities. |
| doi_str_mv | 10.1073/pnas.2021785118 |
| format | Article |
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ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SARS-CoV-2 ORF8 was determined at 2.04-Å resolution by X-ray crystallography. The structure reveals a ∼60-residue core similar to SARS-CoV-2 ORF7a, with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. A covalent disulfide-linked dimer is formed through an N-terminal sequence specific to SARS-CoV-2, while a separate noncovalent interface is formed by another SARS-CoV-2−specific sequence, 73YIDI76. Together, the presence of these interfaces shows how SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2021785118</identifier><identifier>PMID: 33361333</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>BASIC BIOLOGICAL SCIENCES ; Biological Sciences ; Coronaviruses ; COVID-19 ; Crystal structure ; Crystallography ; Dimerization ; Dimers ; Evolution ; Evolution, Molecular ; Immune Evasion ; Immune response ; INAUGURAL ARTICLES ; Interfaces ; Molecular Structure ; Proteins ; SARS-CoV-2 ; SARS-CoV-2 - chemistry ; Severe acute respiratory syndrome coronavirus 2 ; Viral diseases ; Viral Proteins - chemistry ; X-ray crystallography</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-01, Vol.118 (2), p.1-6</ispartof><rights>Copyright © 2021 the Author(s). 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| subjects | BASIC BIOLOGICAL SCIENCES Biological Sciences Coronaviruses COVID-19 Crystal structure Crystallography Dimerization Dimers Evolution Evolution, Molecular Immune Evasion Immune response INAUGURAL ARTICLES Interfaces Molecular Structure Proteins SARS-CoV-2 SARS-CoV-2 - chemistry Severe acute respiratory syndrome coronavirus 2 Viral diseases Viral Proteins - chemistry X-ray crystallography |
| title | Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein |
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