Abstract
Lassa virus (LASV) is the most prevalent member of the arenavirus family and the causative agent of Lassa fever, a viral hemorrhagic fever. Although there are annual outbreaks in West Africa, and recently isolated cases worldwide, there are no current therapeutics or vaccines. As such, LASV poses a significant global public health threat. One of the key steps in LASV infection is delivering its genetic material by fusing its viral membrane with the host cell membrane. This process is facilitated by significant conformational changes within glycoprotein 2 (GP2), yielding distinct prefusion and postfusion structural states. However, structural information is missing to understand the changes that occur in the transmembrane domain (TM) during the fusion process. Previously, we showed that the TM undergoes pH-dependent structural changes that result in a helical extension. Here, we provide the 1H, 15N, and 13C assignment of the LASV TM backbone in the prefusion and postfusion states. We also provide the 1H, 15N, and 13C assignment of two mutants, G429P and D432P, which prevent this helical extension. These results will help understand the role the TM plays in membrane fusion and can lead to the design of therapeutics against LASV infection.
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Data availability
The chemical shift information for the wild type LASV TM and mutants was deposited in the BMRB data bank under the following entry numbers: Prefusion wild type TM – 52449; Postfusion wild type TM – 52450; Prefusion TM G429P – 52451; Postfusion TM G429P – 52452; Prefusion TM D432P – 52453; Postfusion TM D432P – 52454.
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Acknowledgements
This work was supported by the University of Maryland startup funds. We would like to thank D. Zhang for assistance with the NMR experiments.
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PMK and JL designed the experiments; PMK prepared the samples and performed all the NMR analyses; PMK and JL wrote the manuscript.
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Keating, P.M., Lee, J. Assignment of the Lassa virus transmembrane domain in the prefusion and postfusion states in detergent micelles. Biomol NMR Assign (2024). https://doi.org/10.1007/s12104-024-10184-4
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DOI: https://doi.org/10.1007/s12104-024-10184-4