Project A02

Principal Investigator

Dr. Jan Kosinski

CSSB Center for Structural Systems Biology
European Molecular Biology Laboratory

A2

PhD candidate

Konstantin Gilep

A2

Project Summary A02

Protein-protein interactions determining influenza A virus (IAV) shape and assembly

Influenza A virus (IAV) poses a significant threat to public health worldwide, with its ability to rapidly evolve and cause seasonal epidemics and occasional pandemics [1]. Understanding the intricate molecular interactions governing IAV shape and assembly is crucial for devising effective therapeutic strategies [2-4]. The ongoing project aims to elucidate the structural basics of spherical and filamentous IAV virions [2]. The project focuses on integrative structural approaches that combine AlphaFold protein structure prediction software [5, 6]  with variable experimental data, including 3D imaging with cryo-electron tomography.

References

  1. Krammer F, Smith GJD, Fouchier RAM, et al. Influenza. Nat Rev Dis Primers. 2018 Jun 28;4(1):3. doi: 10.1038/s41572-018-0002-y.
  2. Dadonaite B, Vijayakrishnan S, Fodor E, et al. Filamentous influenza viruses. J Gen Virol. 2016 Aug;97(8):1755-1764. doi: 10.1099/jgv.0.000535.
  3. Casalino L, Seitz C, Lederhofer J, Tsybovsky Y, Wilson IA, Kanekiyo M, Amaro RE. Breathing and Tilting: Mesoscale Simulations Illuminate Influenza Glycoprotein Vulnerabilities. ACS Cent Sci. 2022 Dec 28;8(12):1646-1663. doi: 10.1021/acscentsci.2c00981.
  4. Peukes J, Dmitrieff S, Nédélec FJ, et al. A physical model for M1-mediated influenza A virus assembly. bioRxiv, 2024, doi: 10.1101/2024.06.01.594783.
  5. Wayment-Steele HK, Ojoawo A, Otten R, et al. Predicting multiple conformations via sequence clustering and AlphaFold2. Nature. 2024 Jan;625(7996):832-839. doi: 10.1038/s41586-023-06832-9.
  6. Abramson J, Adler J, Dunger J, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w.