Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of a potentially fatal disease named coronavirus disease 2019 (COVID-19), has raised significant public health concerns globally. To date, the COVID-19 pandemic has caused millions of people to be infected with SARS-CoV-2 worldwide. It has been known since the 2003 SARS epidemic that coronaviruses (CoVs) have large RNA genomes, the replication of which requires an RNA-dependent RNA replication/transcription complex. CoV nonstructural proteins (Nsps) play pivotal roles in the assembly of this complex and associated enzymatic functions in virus genomic replication. Several smaller nonenzymatic Nsps assist with RNA-dependent RNA polymerase function. In this study, we determined the structure of SARS-CoV-2 nonstructural protein 9 (nsp9), an RNA-binding protein that is essential for CoV replication. Its homotetrameric structure with two stable dimeric interfaces provids a structural basis for understanding the mechanisms of RNA-binding protein self-assembly, which may be essential for the regulation of viral RNA replication and transcription.
Highlights
Coronavirus disease 2019 (COVID-19), an acute respiratory distress syndrome caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is currently a global pandemic that has been spreading across all continents since late 2019 [1,2,3]
In this study, we first revealed the horseshoe-like tetrameric structure of nsp9 encoded by the genomic RNA of SARS-CoV-2
This homotetrameric structure comprised two significant styles of dimeric conformation that were found in nsp9 structures published in the last decade [19, 21]
Summary
Coronavirus disease 2019 (COVID-19), an acute respiratory distress syndrome caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is currently a global pandemic that has been spreading across all continents since late 2019 [1,2,3]. Upon entry into the host cell, the virus expresses its replicase gene to initially generate two precursor polyproteins, pp1a and pp1ab. These undergo cleavage to yield 16 mature nonstructural proteins (nsp1–16) as well as several intermediate precursors by two distinct viral proteinases, the papain-like proteinase within nsp and a 3C-like proteinase nsp5 [11]. These nsps includes replicative enzymes (e.g., nsp12/RdRp, and nsp13/helicase), a variety (2020) 1:5 of subunits performing accessory functions for viral RNA synthesis (e.g., nsp8/primase, nsp14/exoribonuclesae, and nsp15/endoribonuclease NendoU) and several smaller nonenzymatic nsps (nsp, nsp, and nsp10) assist with RNA-dependent RNA polymerase function [12,13,14,15,16,17]
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