Biological Sciences Division
Published May 10, 2021 | Version v1
Journal article Open

2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography

Creators

  • 1. University of Chicago
  • 2. Argonne National Laboratory
  • 3. Northwestern University

Description

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 (m7GpppAm2′-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.

Data availability

Structure data have been deposited in the Protein Data Bank (6XKM, 7JHE, 7JPE, and 7JIB) (47–50).

Files

wilamowski-et-al-2021-2-o-methylation-of-rna-cap-in-sars-cov-2-captured-by-serial-crystallography.pdf

Files (12.3 MB)

Additional details

Identifiers

DOI
10.1073/pnas.2100170118
Other
oai:uchicago.tind.io:9658

Funding

National Institute of Allergy and Infectious Diseases
HHSN272201700060C
CARES Act
Department of Energy
DE-AC02-06CH11357

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Biochemistry and Molecular Biology