Vaccinia Virus Proteins A52 and B14 Share a Bcl-2–Like Fold but Have Evolved to Inhibit NF-κB rather than Apoptosis
2008

Vaccinia Virus Proteins A52 and B14: Structure and Function

publication 10 minutes Evidence: high

Author Information

Author(s): Graham Stephen C., Bahar Mohammad W., Cooray Samantha, Chen Ron A.-J., Whalen Daniel M., Abrescia Nicola G. A., Alderton David, Owens Raymond J., Stuart David I., Smith Geoffrey L., Grimes Jonathan M.

Primary Institution: The Division of Structural Biology and the Oxford Protein Production Facility, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

Hypothesis

How do the vaccinia virus proteins A52 and B14 inhibit NF-κB activation?

Conclusion

The study reveals that A52 and B14 share a Bcl-2-like fold but do not regulate apoptosis; instead, they inhibit NF-κB activation.

Supporting Evidence

  • A52 and B14 inhibit NF-κB activation in response to various stimuli.
  • Both proteins adopt a Bcl-2-like fold despite low sequence similarity.
  • A52 and B14 do not have a binding groove for pro-apoptotic peptides.
  • Structure-based phylogenetic analysis shows poxvirus Bcl-2-like proteins are more similar to each other than to cellular Bcl-2-like proteins.

Takeaway

Vaccinia virus has special proteins that help it avoid being attacked by the immune system. Two of these proteins, A52 and B14, look like a family of proteins that usually help cells die, but instead, they help the virus survive.

Methodology

The crystal structures of A52 and B14 were solved using multiple-wavelength anomalous dispersion (MAD) experiments.

Limitations

The precise molecular interactions of A52 and B14 with host proteins require further experimental confirmation.

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000128

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication