UV radiation induces genome-mediated, site-specific cleavage in viral proteins

Krista Rule Wigginton1, Laure Menin, Therese Sigstam

  • 1Laboratory of Environmental Chemistry, School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

Insights

UV light causes specific virus protein cleavage through a genome-mediated pathway. Viral RNA is essential for this process, which involves radical formation at Cys46-Ser47.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Understanding UV damage to biomolecules is crucial, but specific pathways remain unclear.
  • Viral protein structure and function can be affected by external factors like UV radiation.

Purpose of the Study:

  • To elucidate the mechanism of site-specific virus protein cleavage induced by UV irradiation.
  • To investigate the role of the viral genome in UV-induced protein damage.

Main Methods:

  • UV irradiation (254 nm) of bacteriophage MS2.
  • Mass spectrometry (ESI-, MALDI-FT-ICR, Orbitrap, TOF) for protein damage characterization.
  • Computational QM/MM studies to confirm radical mechanism.

Main Results:

  • Identified Cys46-Ser47 backbone cleavage site in MS2 capsid protein.
  • Demonstrated essential role of viral RNA in inducing cleavage.
  • Proposed a radical formation mechanism involving Cys46 oxidation and Ser47 hydrogen abstraction.
  • Observed no site-specific cleavage in bacteriophage GA.

Conclusions:

  • A novel genome-mediated mechanism for UV-induced, site-specific protein cleavage is described.
  • This process occurs without external sensitizers, highlighting a unique interaction between viral RNA and protein.
  • The findings provide new insights into viral response to UV damage.

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