Significance The structure of the SARS-CoV-2 ORF8 protein reveals two novel intermolecular interfaces layered onto an ORF7 fold. One is mediated by a disulfide bond, the other is noncovalent, and both are novel with respect to SARS-CoV. The structural analysis here establishes a molecular framework for understanding the rapid evolution of ORF8, its contributions to COVID-19 pathogenesis, and the potential for its neutralization by antibodies. 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.
【저자키워드】 COVID-19, SARS-CoV-2, X-ray crystallography, 【초록키워드】 Evolution, antibodies, coronavirus, SARS-CoV, neutralization, severity, COVID-19 disease, Spread, Protein, COVID-19 pathogenesis, ORF8, immune responses, molecular, Immune suppression, ORF7a, ORF8 protein, Structural analysis, disulfide bond, acute respiratory syndrome, sequence, activities, molecular basis, N-terminal, caused, addition, was determined, unique, interfere, reveal, Significance, the SARS-CoV-2, 【제목키워드】 Structure, Protein, immune evasion, ORF8,