Open AccessStructure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein
Author(s) -
Thomas G Flower,
Cosmo Z. Buffalo,
Richard M. Hooy,
Marc Allaire,
Xuefeng Ren,
James H. Hurley
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2021785118
Subject(s) - antibody , immune system , evasion (ethics) , covid-19 , pathogenesis , disulfide bond , neutralization , biology , intermolecular force , antigen antibody complex , chemistry , virology , biochemistry , immunology , medicine , molecule , disease , organic chemistry , pathology , outbreak , infectious disease (medical specialty)
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, 73 YIDI 76 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.