title: SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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
  Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.
authors.affiliation: State Research Center of Virology and Biotechnology "Vector" Rospotrebnadzor, Novosibirsk region, Koltsovo, Russian Federation. antonec@yandex.ru.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Antonets
authors.forename: Tatyana S
authors.initials: TS
authors.lastname: Nepomnyashchikh
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Shchelkunov