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bioRxiv · 10.1101/2020.08.27.270637

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

Flower, T. G.·Buffalo, C. Z.·Hooy, R. M.·Allaire, M.·Ren, X.·Hurley, J. H.
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Abstract

The molecular basis for the severity and rapid spread of the COVID-19 disease caused by 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 [A] resolution by x-ray crystallography. The structure reveals a ~60 residue core similar to SARS-CoV 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 non-covalent 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.

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Flower, T. G., Buffalo, C. Z., Hooy, R. M., Allaire, M., Ren, X., Hurley, J. H.. 2020-08-27. Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion. https://doi.org/10.1101/2020.08.27.270637

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