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Poxvirus A46 protein binds to TIR domain-containing Mal/TIRAP via an α-helical sub-domain

Shun-Ichiro Oda1, Edward Franklin, Amir R Khan

  • 1School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.

Molecular Immunology
|August 12, 2011
PubMed

Insights

Vaccinia virus protein A46, crucial for subverting host immunity, has a dimeric alpha-helical C-terminus that binds to Mal adaptor proteins. This finding offers new insights into poxvirus immune evasion strategies.

Area of Science:

  • Virology
  • Immunology
  • Structural Biology

Background:

  • Poxviruses, like vaccinia virus, are large DNA viruses that replicate in the cytosol.
  • They express proteins, such as A46, to counteract host immune responses.
  • The Toll-like/interleukin-1 receptor (TLR) pathway is a key component of innate immunity targeted by viral proteins.

Purpose of the Study:

  • To investigate the structural and binding properties of vaccinia virus protein A46.
  • To elucidate the mechanism by which A46 interacts with host immune signaling adaptors.
  • To provide a biophysical analysis of poxvirus protein-TIR domain interactions.

Main Methods:

  • Experimental determination of the C-terminal structure of A46.
  • Biophysical analysis of A46's interaction with the Mal adaptor protein.
  • In vitro studies using peptide fragments of A46 (VIPER).

Main Results:

  • The C-terminus of A46 forms a dimeric alpha-helical structure.
  • This dimeric C-terminus retains the ability to bind to monomeric Mal.
  • A peptide fragment, VIPER, previously shown to be biologically active, did not interact with Mal in vitro.

Conclusions:

  • The study provides the first biophysical characterization of a poxvirus protein binding to a Toll-like/interleukin-1 receptor pathway adaptor.
  • The dimeric alpha-helical C-terminus of A46 is critical for its interaction with Mal.
  • These findings enhance our understanding of viral immune evasion mechanisms mediated by poxviruses.

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