Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes.
Coronaviruses infect many different species including humans. The last two decades have seen three zoonotic coronaviruses, with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing a pandemic in 2020. Coronaviral non-structural proteins (nsps) form the replication-transcription complex (RTC). Nsp7 and nsp8 interact with and regulate the RNA-dependent RNA-polymerase and other ... enzymes in the RTC. However, the structural plasticity of nsp7+8 complexes has been under debate. Here, we present the framework of nsp7+8 complex stoichiometry and topology based on native mass spectrometry and complementary biophysical techniques of nsp7+8 complexes from seven coronaviruses in the genera Alpha- and Betacoronavirus including SARS-CoV-2. Their complexes cluster into three groups, which systematically form either heterotrimers or heterotetramers or both, exhibiting distinct topologies. Moreover, even at high protein concentrations, SARS-CoV-2 nsp7+8 consists primarily of heterotetramers. From these results, the different assembly paths can be pinpointed to specific residues and an assembly model proposed.
Mesh Terms:
Alphacoronavirus, Amino Acid Sequence, Betacoronavirus, Conserved Sequence, Cross-Linking Reagents, Models, Molecular, Protein Multimerization, Protein Subunits, Scattering, Radiation, Scattering, Small Angle, Species Specificity, Viral Nonstructural Proteins, X-Ray Diffraction
Alphacoronavirus, Amino Acid Sequence, Betacoronavirus, Conserved Sequence, Cross-Linking Reagents, Models, Molecular, Protein Multimerization, Protein Subunits, Scattering, Radiation, Scattering, Small Angle, Species Specificity, Viral Nonstructural Proteins, X-Ray Diffraction
Sci Adv
Date: Mar. 01, 2021
PubMed ID: 33658206
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