Open Access2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
Author(s) -
Mateusz Wilamowski,
D.A. Sherrell,
G. Minasov,
Young Chang Kim,
L. Shuvalova,
Alex Lavens,
Ryan Chard,
N. Maltseva,
R. Jedrzejczak,
Mónica RosasLemus,
Nickolaus Saint,
Ian Foster,
K. Michalska,
K.J.F. Satchell,
A. Joachimiak
Publication year - 2021
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.2100170118
Subject(s) - methylation , methyltransferase , rna , chemistry , methionine , covid-19 , messenger rna , crystal structure , crystallography , stereochemistry , microbiology and biotechnology , virology , biology , biochemistry , medicine , dna , disease , amino acid , pathology , infectious disease (medical specialty) , gene
The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5'-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2'-O position of the first nucleotide. To investigate the conformational changes of the complex during 2'-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog ( m7 GpppA m2'-O ). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.