The nucleotide addition cycle of the SARS-CoV-2 polymerase

Bera SC, Seifert M, Kirchdoerfer RN, Van Nies P, YIBULAYIN W, Quack S, Papini FS, Arnold JJ, Canard B, Cameron CE, Depken M, Dulin D (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 36

Article Number: 109650

Journal Issue: 9

DOI: 10.1016/j.celrep.2021.109650

Abstract

Coronaviruses have evolved elaborate multisubunit machines to replicate and transcribe their genomes. Central to these machines are the RNA-dependent RNA polymerase subunit (nsp12) and its intimately associated cofactors (nsp7 and nsp8). We use a high-throughput magnetic-tweezers approach to develop a mechanochemical description of this core polymerase. The core polymerase exists in at least three catalytically distinct conformations, one being kinetically consistent with incorporation of incorrect nucleotides. We provide evidence that the RNA-dependent RNA polymerase (RdRp) uses a thermal ratchet instead of a power stroke to transition from the pre- to post-translocated state. Ultra-stable magnetic tweezers enable the direct observation of coronavirus polymerase deep and long-lived backtracking that is strongly stimulated by secondary structures in the template. The framework we present here elucidates one of the most important structure-dynamics-function relationships in human health today and will form the grounds for understanding the regulation of this complex.

Authors with CRIS profile

Subhas Chandra Bera Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin Mona Seifert Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin WUBULIKASIMU YIBULAYIN Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin Salina Quack Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin David Dulin Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin

Involved external institutions

Delft University of Technology (TU Delft) NL Netherlands (NL) University of North Carolina at Chapel Hill US United States (USA) (US) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) FR France (FR) University of Wisconsin - Madison US United States (USA) (US)

How to cite

APA:

Bera, S.C., Seifert, M., Kirchdoerfer, R.N., Van Nies, P., YIBULAYIN, W., Quack, S.,... Dulin, D. (2021). The nucleotide addition cycle of the SARS-CoV-2 polymerase. Cell Reports, 36(9). https://doi.org/10.1016/j.celrep.2021.109650

MLA:

Bera, Subhas Chandra, et al. "The nucleotide addition cycle of the SARS-CoV-2 polymerase." Cell Reports 36.9 (2021).

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