Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

Protein Sci. 2020 Jul;29(7):1596-1605. doi: 10.1002/pro.3873. Epub 2020 May 2.

Abstract

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS-CoVs and Middle East Respiratory Syndrome coronavirus (MERS-CoVs), the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.

Keywords: COVID-19; EndoU family; NendoU; Nsp15; SARS-CoV-2; crystal structure; endoribonuclease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Betacoronavirus / chemistry*
  • Betacoronavirus / genetics
  • Betacoronavirus / metabolism
  • Catalytic Domain
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Endoribonucleases / chemistry*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / chemistry*
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / metabolism
  • Models, Molecular
  • Oligonucleotides / chemistry*
  • Oligonucleotides / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SARS Virus / chemistry*
  • SARS Virus / genetics
  • SARS Virus / metabolism
  • SARS-CoV-2
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism

Substances

  • Oligonucleotides
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • Endoribonucleases
  • nidoviral uridylate-specific endoribonuclease