Thursday, March 14, 2024
12:30 - 14:00
12:30 - 12:50 Pim America (PLS) - PhD Candidate, Vrije Universiteit Amsterdam
Two coronavirus helicases bind the polymerase sequentially and the second speeds up RNA synthesis
Abstract: The SARS-CoV-2 pandemic has had a profound impact on humanity, underscoring the urgent need for therapeutics against this class of viruses. To address this, a deep understanding of coronavirus molecular biology and biochemistry is essential. In this study, we focused on exploring the role of nsp13-helicase in the dynamics of SARS-CoV-2 RNA synthesis within the functional complex of the replication-transcription complex (RTC). Nsp13-helicase is essential for the virus to replicate, but its functional role remains unknown. The nsp13-helicase has an opposite polarity to nsp12-polymerase, and whether nsp13-helicase supports RTC RNA synthesis, how it provides such supports remain unclear. To shed light on nsp13-helicase functional role in RNA synthesis, we employed a high-throughput magnetic tweezers assay to monitor CoV RTC RNA synthesis at the single-molecule level under a constant force. We found that, in the presence of nsp13-helicase, the RTC exhibits bursts of very fast nucleotide addition and fewer pausing compared to the core RTC (consisting of nsp12-polymerase with co-factors nsp7 and nsp8). Furthermore, we show that nsp13-helicase association with the CoV polymerase is specific, and support replication through RNA secondary structures by unwinding the template strand from the complementary non-template strand. We obtained the energy landscape of nsp13-helicase association with the RTC and derived a precise model of the nucleotide addition dynamics in the presence of nsp13-helicase. We tested this model for nsp13-helicase concentration and the applied force sweeps. Our work is the first functional characterization of the role of nsp13-helicace in CoV replication.
12:50 -13:45 - Prof. Dr. Elina Fuchs (CERN, Hannover)
Biography
She is in particular interested in scenarios of New Physics that can be discovered or constrained at the LHC and future colliders, with atomic precision spectroscopy, or with cosmological observations. As the coordinator of the theory branch of the CERN Quantum Technology Initiative (QTI, https://quantum.cern/), she looks forward to hearing from you if you are interested in getting involved in projects or discussions on quantum sensing, quantum computing or quantum theory. Fuchs, Elina | Department of Theoretical Physics (theory.cern)
VU
WN Building
M129
Colloquium
astrophysics, gravitational and astroparticle physics
Prof. Dr. Elina Fuchs and Pim America