Variola virus (VARV) the causative agent of
smallpox, eradicated in 1980, have wide spectrum of immunomodulatory
proteins to evade host immunity. Recently additional
biological activity was discovered for VARV CrmB
protein, known to bind and inhibit tumour
necrosis factor (TNF) through its N-terminal domain homologous to cellular
TNF receptors. Besides binding TNF, this
protein was also shown to bind with high affinity several
chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind
chemokines was shown to be associated with unique C-terminal domain of CrmB
protein. This domain named SECRET (Smallpox virus-Encoded
Chemokine Receptor) is unrelated to the host
proteins and lacks significant homology with other known viral
chemokine-
binding proteins or any other known
protein.
FINDINGS: De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus
CC-chemokine binding protein (vCCI) and vaccinia virus A41
protein, despite low sequence identity between these three
proteins. Potential
ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral
chemokine-
binding proteins.
CONCLUSIONS: