The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2′-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2′- O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2′- O methylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain. The SARS-CoV-2 nsp16/nsp10 enzyme complex methylates the 2′-OH of the first nucleotide of the viral mRNA, converting the Cap-0 to Cap-1, which helps the virus to evade immune surveillance in the host cell. Here, the authors present the crystal structure of SARS-CoV-2 nsp16/nsp10 with the bound Cap-1 RNA nucleotide product and a post-release SAH containing structure.
【저자키워드】 X-ray crystallography, Multienzyme complexes, 【초록키워드】 Structure, SARS-CoV-2, SARS-CoV, virus, immune, RNA, Surveillance, outbreak, mRNA, binding, Methylation, nucleotide, conformational change, host cells, host cell, enzymatic activity, enzyme, complex, help, variant of SARS-CoV-2, observé, identify, unique, transcribed, representing, evade, modify, convert, twisting, 【제목키워드】 SARS-CoV-2, mRNA, Methylation, nucleotide,