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Molecular Basis of the pH-Controlled Maturation of the Tick-Borne Encephalitis Flavivirus
Emmanuelle Bignon1, Elise Dumont2,3, Antonio Monari4
1Université de Lorraine and CNRS, UMR 7019 LPCT, F-5400, Nancy, France.
Abstract:
Flaviviruses are enveloped viruses causing high public concerns. Their maturation spans several cellular compartments having different pH. Thus, complex control mechanisms are in place to avoid premature maturation. Here we report the dynamical behavior at neutral and acidic pH of the precursor of the membrane fusion protein E of tick-borne encephalitis, showing the different stabilizations of the E dimer and the role played by the small fusion-assisting protomer (pr). The comprehension, at atomic resolution, of the fine regulation of viral maturation will be fundamental to the development of efficient strategies against emerging viral threats.
Insights
Researchers studied the tick-borne encephalitis virus
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Flaviviruses are enveloped viruses that pose significant public health risks.
- Viral maturation involves multiple cellular compartments with varying pH levels.
- Complex regulatory mechanisms prevent premature flavivirus maturation.
Purpose of the Study:
- To investigate the pH-dependent dynamical behavior of the tick-borne encephalitis virus (TBEV) precursor membrane fusion protein E.
- To elucidate the stabilization of the E dimer and the role of the fusion-assisting protomer (pr) during maturation.
Main Methods:
- Analysis of the dynamical behavior of the TBEV E protein precursor at neutral and acidic pH.
- Atomic resolution investigation of protein stabilization and interactions.
Main Results:
- The TBEV E protein precursor exhibits distinct stabilization patterns at neutral and acidic pH.
- The small fusion-assisting protomer (pr) plays a crucial role in regulating viral maturation.
Conclusions:
- Understanding the atomic-level regulation of viral maturation is key to combating emerging viral threats.
- Detailed knowledge of TBEV E protein dynamics can inform the development of novel antiviral strategies.
