In order to replicate, viruses must hijack host cell signaling pathways, one of the most important being apoptosis. Poxviridae have evolved to mimic specific cellular proteins including those of the Bcl-2 family, which are responsible for regulation of the intrinsic apoptotic pathway.
Infection by Vaccinia virus, a poxviridae member, is generally mild and asymptomatic generating cross reactivity to the highly fatal small poxvirus, Variola virus, and has been the focus of much research. The F1L open reading frame of both Variola and Vaccinia encodes a virulence protein that shows significant structurally homology to Bcl-2 despite having low sequence identity. In recent research the Vaccinia derived F1L protein has been suggested to play a role in Caspase 9 inhibition via a helical N-terminal region.
To date the Variola viral F1L N-terminal region has yet to be structurally resolved. To characterise this region and its interactions we embarked on in-solution structural studies using small-angle X-ray scattering and analysing binding interactions with known cell death regulators.
We show that the F1L N-terminal region is unstructured in solution and neither displays Caspase 9 inhibitory activity or is important for F1L’s anti-apoptotic activity.