Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes
- Krichel, Boris
- Bylapudi, Ganesh
- Schmidt, Christina
- Blanchet, Clement
- Schubert, Robin
- Brings, Lea
- Koehler, Martin
- Zenobi, Renato
- Svergun, Dmitri
- Lorenzen, Kristina
- Madhugiri, Ramakanth
- Ziebuhr, John
- Uetrecht, Charlotte ORCID
English
Abstract Coronaviruses infect many different species including humans. The last two decades have seen three zoonotic coronaviruses with SARS-CoV-2 causing a pandemic in 2020. Coronaviral non-structural proteins (nsp) built up 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 complex has been under debate. Here, we present the framework of nsp7+8 complex stoichiometry and topology based on a 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 mainly heterotetramers are observed for SARS-CoV-2 nsp7+8. From these results, the different assembly paths can be pinpointed to specific residues and an assembly model is proposed.
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- https://sonar.ch/global/documents/274222
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