Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein

Flower, Thomas G.; Buffalo, Cosmo Z.; Hooy, Richard M.; Allaire, Marc; Ren, Xuefeng; Hurley, James H.

doi:10.1073/pnas.2021785118

Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein

Journal Article · Tue Dec 22 23:00:00 EST 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2021785118· OSTI ID:1815732

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Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology, California Inst. for Quantitative Biosciences; OSTI
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology, California Inst. for Quantitative Biosciences
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology, California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1815732

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 2 Vol. 118; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (25)

Genomic variance of the 2019‐nCoV coronavirus Ceraolo, Carmine; Giorgi, Federico M. Journal of Medical Virology, Vol. 92, Issue 5 https://doi.org/10.1002/jmv.25700	journal	February 2020
Using Dali for Protein Structure Comparison Holm, Liisa Methods in Molecular Biology https://doi.org/10.1007/978-1-0716-0270-6_3	book	January 2020
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Lu, Roujian; Zhao, Xiang; Li, Juan The Lancet, Vol. 395, Issue 10224 https://doi.org/10.1016/S0140-6736(20)30251-8	journal	February 2020
Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study Young, Barnaby E.; Fong, Siew-Wai; Chan, Yi-Hao The Lancet, Vol. 396, Issue 10251 https://doi.org/10.1016/S0140-6736(20)31757-8	journal	August 2020
Mortality in COVID-19 disease patients: Correlating the association of major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants de Sousa, Eric; Ligeiro, Dário; Lérias, Joana R. International Journal of Infectious Diseases, Vol. 98 https://doi.org/10.1016/j.ijid.2020.07.016	journal	September 2020
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Laha, Sayantan; Chakraborty, Joyeeta; Das, Shantanab Infection, Genetics and Evolution, Vol. 85 https://doi.org/10.1016/j.meegid.2020.104445	journal	November 2020
Structure and Intracellular Targeting of the SARS-Coronavirus Orf7a Accessory Protein Nelson, Christopher A.; Pekosz, Andrew; Lee, Chung A. Structure, Vol. 13, Issue 1 https://doi.org/10.1016/j.str.2004.10.010	journal	January 2005
The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway Li, Jin-Yan; Liao, Ce-Heng; Wang, Qiong Virus Research, Vol. 286 https://doi.org/10.1016/j.virusres.2020.198074	journal	September 2020
Origin and evolution of pathogenic coronaviruses Cui, Jie; Li, Fang; Shi, Zheng-Li Nature Reviews Microbiology, Vol. 17, Issue 3 https://doi.org/10.1038/s41579-018-0118-9	journal	December 2018
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Gordon, David E.; Jang, Gwendolyn M.; Bouhaddou, Mehdi Nature, Vol. 583, Issue 7816 https://doi.org/10.1038/s41586-020-2286-9	journal	April 2020
ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection Hachim, Asmaa; Kavian, Niloufar; Cohen, Carolyn A. Nature Immunology, Vol. 21, Issue 10 https://doi.org/10.1038/s41590-020-0773-7	journal	August 2020
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission Muth, Doreen; Corman, Victor Max; Roth, Hanna Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-33487-8	journal	October 2018
SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East Gong, Yu-Nong; Tsao, Kuo-Chien; Hsiao, Mei-Jen Emerging Microbes & Infections, Vol. 9, Issue 1 https://doi.org/10.1080/22221751.2020.1782271	journal	January 2020
The EMBL-EBI search and sequence analysis tools APIs in 2019 Madeira, Fábio; Park, Young mi; Lee, Joon Nucleic Acids Research, Vol. 47, Issue W1 https://doi.org/10.1093/nar/gkz268	journal	April 2019
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
The CCP4 suite programs for protein crystallography No authors listed Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
Real-space refinement in PHENIX for cryo-EM and crystallography Afonine, Pavel V.; Poon, Billy K.; Read, Randy J. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 6 https://doi.org/10.1107/S2059798318006551	journal	May 2018
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms Gordon, David E.; Hiatt, Joseph; Bouhaddou, Mehdi Science, Vol. 370, Issue 6521 https://doi.org/10.1126/science.abe9403	journal	December 2020
Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination Lau, Susanna K. P.; Feng, Yun; Chen, Honglin Journal of Virology, Vol. 89, Issue 20 https://doi.org/10.1128/JVI.01048-15	journal	August 2015
Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses Tan, Yongjun; Schneider, Theresa; Leong, Matthew mBio, Vol. 11, Issue 3 https://doi.org/10.1128/mBio.00760-20	journal	June 2020
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2 Su, Yvonne C. F.; Anderson, Danielle E.; Young, Barnaby E. mBio, Vol. 11, Issue 4 https://doi.org/10.1128/mBio.01610-20	journal	August 2020
SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence Mohammad, Sameer; Bouchama, Abderrezak; Mohammad Alharbi, Bothina Pathogens, Vol. 9, Issue 9 https://doi.org/10.3390/pathogens9090677	journal	August 2020

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