Journalartikel

Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes


AutorenlisteKrichel, 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

Jahr der Veröffentlichung2021

ZeitschriftScience Advances

Bandnummer7

Heftnummer10

ISSN2375-2548

Open Access StatusGold

DOI Linkhttps://doi.org/10.1126/sciadv.abf1004

VerlagAmerican Association for the Advancement of Science


Abstract
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.



Zitierstile

Harvard-ZitierstilKrichel, B., Bylapudi, G., Schmidt, C., Blanchet, C., Schubert, R., Brings, L., et al. (2021) Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes, Science Advances, 7(10), Article eabf1004. https://doi.org/10.1126/sciadv.abf1004

APA-ZitierstilKrichel, B., Bylapudi, G., Schmidt, C., Blanchet, C., Schubert, R., Brings, L., Koehler, M., Zenobi, R., Svergun, D., Lorenzen, K., Madhugiri, R., Ziebuhr, J., & Uetrecht, C. (2021). Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes. Science Advances. 7(10), Article eabf1004. https://doi.org/10.1126/sciadv.abf1004



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