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

Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2021785118. doi: 10.1073/pnas.2021785118.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; X-ray crystallography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Evolution, Molecular
  • Immune Evasion
  • Molecular Structure*
  • SARS-CoV-2 / chemistry*
  • Viral Proteins / chemistry*

Substances

  • ORF8 protein, SARS-CoV-2
  • Viral Proteins